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CHEMISTRY (595 journals)                  1 2 3 | Last

Showing 1 - 200 of 735 Journals sorted alphabetically
2D Materials     Hybrid Journal   (Followers: 8)
Accreditation and Quality Assurance: Journal for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 26)
ACS Catalysis     Full-text available via subscription   (Followers: 34)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 18)
ACS Combinatorial Science     Full-text available via subscription   (Followers: 23)
ACS Macro Letters     Full-text available via subscription   (Followers: 24)
ACS Medicinal Chemistry Letters     Full-text available via subscription   (Followers: 39)
ACS Nano     Full-text available via subscription   (Followers: 245)
ACS Photonics     Full-text available via subscription   (Followers: 11)
ACS Synthetic Biology     Full-text available via subscription   (Followers: 21)
Acta Chemica Iasi     Open Access   (Followers: 2)
Acta Chimica Sinica     Full-text available via subscription   (Followers: 1)
Acta Chimica Slovaca     Open Access   (Followers: 1)
Acta Chromatographica     Full-text available via subscription   (Followers: 9)
Acta Facultatis Medicae Naissensis     Open Access  
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 5)
Acta Scientifica Naturalis     Open Access   (Followers: 2)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 5)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 8)
Adsorption Science & Technology     Full-text available via subscription   (Followers: 5)
Advanced Functional Materials     Hybrid Journal   (Followers: 51)
Advanced Science Focus     Free   (Followers: 3)
Advances in Chemical Engineering and Science     Open Access   (Followers: 56)
Advances in Chemical Science     Open Access   (Followers: 13)
Advances in Chemistry     Open Access   (Followers: 15)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18)
Advances in Drug Research     Full-text available via subscription   (Followers: 22)
Advances in Enzyme Research     Open Access   (Followers: 9)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 8)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 16)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 9)
Advances in Materials Physics and Chemistry     Open Access   (Followers: 21)
Advances in Nanoparticles     Open Access   (Followers: 15)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15)
Advances in Polymer Science     Hybrid Journal   (Followers: 41)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 17)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Science and Technology     Full-text available via subscription   (Followers: 12)
African Journal of Bacteriology Research     Open Access  
African Journal of Chemical Education     Open Access   (Followers: 2)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 7)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
AMB Express     Open Access   (Followers: 1)
Ambix     Hybrid Journal   (Followers: 3)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 67)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 14)
American Journal of Chemistry     Open Access   (Followers: 27)
American Journal of Plant Physiology     Open Access   (Followers: 14)
American Mineralogist     Hybrid Journal   (Followers: 14)
Analyst     Full-text available via subscription   (Followers: 40)
Angewandte Chemie     Hybrid Journal   (Followers: 194)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 219)
Annales UMCS, Chemia     Open Access   (Followers: 1)
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 4)
Annual Reports in Computational Chemistry     Full-text available via subscription   (Followers: 3)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 4)
Annual Reports Section B (Organic Chemistry)     Full-text available via subscription   (Followers: 8)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 12)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 15)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antiviral Chemistry and Chemotherapy     Hybrid Journal  
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7)
Applied Spectroscopy     Full-text available via subscription   (Followers: 23)
Applied Surface Science     Hybrid Journal   (Followers: 28)
Arabian Journal of Chemistry     Open Access   (Followers: 6)
ARKIVOC     Open Access   (Followers: 2)
Asian Journal of Biochemistry     Open Access   (Followers: 1)
Atomization and Sprays     Full-text available via subscription   (Followers: 4)
Australian Journal of Chemistry     Hybrid Journal   (Followers: 7)
Autophagy     Hybrid Journal   (Followers: 2)
Avances en Quimica     Open Access   (Followers: 1)
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Biochemistry     Full-text available via subscription   (Followers: 310)
Biochemistry Insights     Open Access   (Followers: 6)
Biochemistry Research International     Open Access   (Followers: 6)
BioChip Journal     Hybrid Journal  
Bioinorganic Chemistry and Applications     Open Access   (Followers: 9)
Bioinspired Materials     Open Access   (Followers: 5)
Biointerface Research in Applied Chemistry     Open Access   (Followers: 2)
Biointerphases     Open Access   (Followers: 1)
Biology, Medicine, & Natural Product Chemistry     Open Access   (Followers: 1)
Biomacromolecules     Full-text available via subscription   (Followers: 19)
Biomass Conversion and Biorefinery     Partially Free   (Followers: 10)
Biomedical Chromatography     Hybrid Journal   (Followers: 6)
Biomolecular NMR Assignments     Hybrid Journal   (Followers: 3)
BioNanoScience     Partially Free   (Followers: 5)
Bioorganic & Medicinal Chemistry     Hybrid Journal   (Followers: 118)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 91)
Bioorganic Chemistry     Hybrid Journal   (Followers: 10)
Biopolymers     Hybrid Journal   (Followers: 18)
Biosensors     Open Access   (Followers: 2)
Biotechnic and Histochemistry     Hybrid Journal   (Followers: 1)
Bitácora Digital     Open Access  
Boletin de la Sociedad Chilena de Quimica     Open Access  
Bulletin of the Chemical Society of Ethiopia     Open Access   (Followers: 2)
Bulletin of the Chemical Society of Japan     Full-text available via subscription   (Followers: 24)
Bulletin of the Korean Chemical Society     Hybrid Journal   (Followers: 1)
C - Journal of Carbon Research     Open Access   (Followers: 3)
Cakra Kimia (Indonesian E-Journal of Applied Chemistry)     Open Access  
Canadian Association of Radiologists Journal     Full-text available via subscription   (Followers: 3)
Canadian Journal of Chemistry     Hybrid Journal   (Followers: 10)
Canadian Mineralogist     Full-text available via subscription   (Followers: 4)
Carbohydrate Research     Hybrid Journal   (Followers: 26)
Carbon     Hybrid Journal   (Followers: 66)
Catalysis for Sustainable Energy     Open Access   (Followers: 7)
Catalysis Reviews: Science and Engineering     Hybrid Journal   (Followers: 8)
Catalysis Science and Technology     Free   (Followers: 7)
Catalysis Surveys from Asia     Hybrid Journal   (Followers: 3)
Catalysts     Open Access   (Followers: 8)
Cellulose     Hybrid Journal   (Followers: 7)
Cereal Chemistry     Full-text available via subscription   (Followers: 4)
ChemBioEng Reviews     Full-text available via subscription   (Followers: 1)
ChemCatChem     Hybrid Journal   (Followers: 8)
Chemical and Engineering News     Free   (Followers: 14)
Chemical Bulletin of Kazakh National University     Open Access  
Chemical Communications     Full-text available via subscription   (Followers: 72)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 24)
Chemical Research in Chinese Universities     Hybrid Journal   (Followers: 3)
Chemical Research in Toxicology     Full-text available via subscription   (Followers: 20)
Chemical Reviews     Full-text available via subscription   (Followers: 182)
Chemical Science     Open Access   (Followers: 22)
Chemical Technology     Open Access   (Followers: 16)
Chemical Vapor Deposition     Hybrid Journal   (Followers: 5)
Chemical Week     Full-text available via subscription   (Followers: 8)
Chemie in Unserer Zeit     Hybrid Journal   (Followers: 58)
Chemie-Ingenieur-Technik (Cit)     Hybrid Journal   (Followers: 26)
ChemInform     Hybrid Journal   (Followers: 8)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 6)
Chemistry & Biology     Full-text available via subscription   (Followers: 30)
Chemistry & Industry     Hybrid Journal   (Followers: 5)
Chemistry - A European Journal     Hybrid Journal   (Followers: 147)
Chemistry - An Asian Journal     Hybrid Journal   (Followers: 15)
Chemistry and Materials Research     Open Access   (Followers: 20)
Chemistry Central Journal     Open Access   (Followers: 4)
Chemistry Education Research and Practice     Free   (Followers: 5)
Chemistry in Education     Open Access   (Followers: 9)
Chemistry International     Hybrid Journal   (Followers: 2)
Chemistry Letters     Full-text available via subscription   (Followers: 44)
Chemistry of Materials     Full-text available via subscription   (Followers: 252)
Chemistry of Natural Compounds     Hybrid Journal   (Followers: 9)
Chemistry World     Full-text available via subscription   (Followers: 22)
Chemistry-Didactics-Ecology-Metrology     Open Access   (Followers: 1)
ChemistryOpen     Open Access   (Followers: 2)
Chemkon - Chemie Konkret, Forum Fuer Unterricht Und Didaktik     Hybrid Journal  
Chemoecology     Hybrid Journal   (Followers: 4)
Chemometrics and Intelligent Laboratory Systems     Hybrid Journal   (Followers: 15)
Chemosensors     Open Access  
ChemPhysChem     Hybrid Journal   (Followers: 9)
ChemPlusChem     Hybrid Journal   (Followers: 2)
ChemTexts     Hybrid Journal  
CHIMIA International Journal for Chemistry     Full-text available via subscription   (Followers: 2)
Chinese Journal of Chemistry     Hybrid Journal   (Followers: 6)
Chinese Journal of Polymer Science     Hybrid Journal   (Followers: 10)
Chromatographia     Hybrid Journal   (Followers: 24)
Clay Minerals     Full-text available via subscription   (Followers: 10)
Cogent Chemistry     Open Access  
Colloid and Interface Science Communications     Open Access  
Colloid and Polymer Science     Hybrid Journal   (Followers: 10)
Colloids and Surfaces B: Biointerfaces     Hybrid Journal   (Followers: 7)
Combinatorial Chemistry & High Throughput Screening     Hybrid Journal   (Followers: 4)
Combustion Science and Technology     Hybrid Journal   (Followers: 18)
Comments on Inorganic Chemistry: A Journal of Critical Discussion of the Current Literature     Hybrid Journal   (Followers: 2)
Composite Interfaces     Hybrid Journal   (Followers: 6)
Comprehensive Chemical Kinetics     Full-text available via subscription   (Followers: 2)
Comptes Rendus Chimie     Full-text available via subscription  
Comptes Rendus Physique     Full-text available via subscription   (Followers: 1)
Computational and Theoretical Chemistry     Hybrid Journal   (Followers: 9)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 12)
Computational Chemistry     Open Access   (Followers: 2)
Computers & Chemical Engineering     Hybrid Journal   (Followers: 9)
Coordination Chemistry Reviews     Full-text available via subscription   (Followers: 3)
Copernican Letters     Open Access   (Followers: 1)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 5)
Crystal Structure Theory and Applications     Open Access   (Followers: 4)
CrystEngComm     Full-text available via subscription   (Followers: 13)
Current Catalysis     Hybrid Journal   (Followers: 2)
Current Metabolomics     Hybrid Journal   (Followers: 5)
Current Opinion in Colloid & Interface Science     Hybrid Journal   (Followers: 9)
Current Opinion in Molecular Therapeutics     Full-text available via subscription   (Followers: 17)
Current Research in Chemistry     Open Access   (Followers: 8)
Current Science     Open Access   (Followers: 61)
Dalton Transactions     Full-text available via subscription   (Followers: 23)
Detection     Open Access   (Followers: 2)
Developments in Geochemistry     Full-text available via subscription   (Followers: 2)
Diamond and Related Materials     Hybrid Journal   (Followers: 12)
Dislocations in Solids     Full-text available via subscription  
Doklady Chemistry     Hybrid Journal  
Drying Technology: An International Journal     Hybrid Journal   (Followers: 4)
Eclética Química     Open Access   (Followers: 1)
Ecological Chemistry and Engineering S     Open Access   (Followers: 3)
Ecotoxicology and Environmental Contamination     Open Access  
Educación Química     Open Access   (Followers: 1)
Education for Chemical Engineers     Hybrid Journal   (Followers: 5)
EJNMMI Radiopharmacy and Chemistry     Open Access  
Elements     Full-text available via subscription   (Followers: 3)
Environmental Chemistry     Hybrid Journal   (Followers: 7)
Environmental Chemistry Letters     Hybrid Journal   (Followers: 4)
Environmental Science & Technology Letters     Full-text available via subscription   (Followers: 5)

        1 2 3 | Last

Journal Cover Biomedical Chromatography
  [SJR: 0.572]   [H-I: 49]   [6 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0269-3879 - ISSN (Online) 1099-0801
   Published by John Wiley and Sons Homepage  [1579 journals]
  • Effects of Tao-Hong-Si-Wu decoction on acute blood stasis in rats based on
           a LC-Q/TOF-MS metabolomics and network approach
    • Authors: Qi Ma; Peng-Ling Li, Yong-Li Hua, Peng Ji, Wan-Ling Yao, Xiao-Song Zhang, Li-Jia Zhong, Yan-Ming Wei
      Abstract: A novel approach using metabolomics coupled with a metabolic network was used to investigate the effects of THSWD on the rat model of acute blood stasis syndrome. Acute blood stasis syndrome was induced by placing the rats in ice-cold water following two injections with epinephrine. The hemorheological indicators (WBV and PV), and the blood coagulation indicators (TT, PT, APTT, and FIB) were detected. The nonparametric univariate method and multivariate statistical analysis were performed for determining the potential biomarkers. A correlation map was structured between biochemical indicators and hub metabolites to explain the effects mechanism of THSWD. After the administration of THSWD, the levels of WBV, PV, TT, APTT, and FIB returned to levels observed in the control group. According to metabolomics coupled with metabolic network analysis, the intervention of THSWD in rats with acute blood stasis syndrome induced substantial and characteristic changes in their metabolic profiles. Fifteen metabolites were screened, which mainly involved ten pathways and five hub metabolites, namely, L-glutamate, L-phenylalanine, N-acylsphingosine, arachidonic acid and phosphatidate. The biochemical indicators and hub metabolites could be adjusted close to normal levels by THSWD. Therefore, combining metabolomics and metabolic network helped evaluate the effects of THSWD on acute blood stasis.
      PubDate: 2017-11-17T09:02:07.472293-05:
      DOI: 10.1002/bmc.4144
  • Determination of Cefoperazone and Sulbactam in serum by HPLC-MS/MS: an
           adapted method for therapeutic drug monitoring in children
    • Authors: Xiu-Jun Wu; Xin Huang, Hai-Yan Shi, Xing-Kai Chen, Qian Dong, Guo-Xiang Hao, Yan Li, Yi Zheng, Wei Zhao
      Abstract: A rapid, accurate and specific high-performance liquid chromatographic -tandem mass spectrometry method has been validated for the simultaneous determination of cefoperazone and sulbactam in a small volume sample for children. A Shim-pack XR-ODS C18 column with gradient elution of water (0.1% formic acid) and acetonitrile (0.1% formic acid) solution was used for separation at a flow rate of 0.3 mL/min. The calibration curves of two analytes in serum showed excellent linearity over the concentration ranges of 0.03-10 μg/mL for cefoperazone, and 0.01-3 μg/mL for sulbactam, respectively. This method involves simple sample preparation steps and was validated according to standard FDA and EMA guidelines in terms of selectivity, linearity, detection limits, matrix effects, accuracy, precision, recovery, and stability. This assay can be easily implemented in clinical practice to determine concentrations of cefoperazone and sulbactam in children.
      PubDate: 2017-11-17T08:10:23.905671-05:
      DOI: 10.1002/bmc.4143
  • Comparative pharmacokinetics study of orientin in rat plasma by
           UHPLC-MS/MS after intravenous administration of single orientin and
           Trollius chinensis Bunge extract
    • Authors: Nan Zhao; Qi Sun, Yang Song, Lin Wang, Tingjian Zhang, Fanhao Meng
      Abstract: Orientin showed a broad array of biological activities, and it is the major bioactive compound in the Trollius chinensis Bunge. Thus, this paper was conducted to investigate the comparative pharmacokinetics of orientin after intravenous administration of single orientin and Trollius chinensis Bunge extract. Sample preparation involved a simple one-step deproteinization procedure with acetonitrile. Chromatographic separation was achieved on a Waters BEH C18 column with a mobile phase consisting of acetonitrile and water containing 0.1% formic acid in an isocratic elution way. The detection was accomplished by multiple reaction monitoring mode with the positive electrospray ionization. The pharmacokinetic properties of orientin were compared after the intravenous administrations of pure orientin and Trollius chinensis Bunge extract to rats with approximately the same dosage of 10mg/kg. Results of the study indicated that the pharmacokinetics of orientin in rat plasma have significant differences between two groups. It is workable on the clinical uses of therapeutic dosing of orientin and Trollius chinensis Bunge.
      PubDate: 2017-11-17T07:16:21.837782-05:
      DOI: 10.1002/bmc.4142
  • Metabolic study of paeoniflorin and total paeony glucosides from Paeoniae
           Radix Rubra in rats by high performance liquid chromatography coupled with
           sequential mass spectrometry (UPLC-ESI-MSn)
    • Authors: Lijun Zhu; Shanshan Sun, Yanxi Hu, Yufeng Liu
      Abstract: A clear understanding of the metabolism of Traditional Chinese Medicine (TCM) is extremely important in their rational clinical application and effective material foundation research. A novel and reliable strategy was performed to find more metabolites of paeoniflorin, determine the metabolites of total paeony glucosides (TPG) by means of determining those metabolites of paeoniflorin, and compare the metabolism differences between paeoniflorin and TPG by intragastric administration. This strategy was characterized as follows: firstly, the rats were divided into two groups (the paeoniflorin group and the TPG group) to find different metabolism mechanism between paeoniflorin and TPG; secondly, UPLC-FT-ICR MS and UPLC-Q-TOF MS2 were applied to obtain accurate molecular weight and structural information respectively; thirdly, the metabolites were tentatively identified by a combination of data-processing methods including mass defect screening, characteristic neutral loss screening and product ion screening; finally, a comparative study was employed in the metabolism of paeoniflorin and TPG. Based on the strategy, eighteen metabolites of paeoniflorin (including four new compounds) and eleven metabolites of TPG (including two new compounds) were identified respectively. In all of the identified metabolites of paeoniflorin, two metabolites in rat plasma, four metabolites in rat urine and six metabolites in rat feces were found for the first time after paeoniflorin administration, respectively. The results indicated that the hydrolyzation of the ester bond and glucosidic band and the conjugation with glucuronide were the major metabolic pathways of paeoniflorin. It has been the first time to detect the metabolites of paeoniflorin and TPG in rats plasma, urine and feces after intragastric administration. The results may contribute to a better understanding of the metabolism mechanism and providing a scientific rationale for researching the material basis of paeoniflorin and TPG in vivo.
      PubDate: 2017-11-17T06:15:46.257061-05:
      DOI: 10.1002/bmc.4141
  • Determination of Telbivudine in the Plasma of Chronic Hepatitis B Patients
           in Long-Term Treatment by High-Performance Liquid Chromatographic-Tandem
           Mass Spectrometry
    • Authors: Bicui Chen; Li Chen, Cai Cheng, Mingkang Zhong, Xiaojin Shi, Jiming Zhang, Bin Wang
      Abstract: Usually, creatine kinase elevation is commonly reported in telbivudine-treated patients. However, little is known abosut the relationship between this adverse drug reaction and plasma concentration. In this study, a sensitive, rapid and safe quantitative bioanalytical method has been established by using LC-MS/MS for the determination of telbivudine in a clinical study of chronic hepatitis B (CHB) patients. The assay was linear in a dynamic 10-10,000 ng/mL range (r2> 0.999) and total analysis time was 6 min in this method. The validated method was applied to quantitatively determine plasma concentration in CHB patients during long-term telbivudine treatment. The results revealed that telbivudine concentration in CK-elevated group (707.92- 2788.78 ng/mL) was significantly higher than those of normal CK (412.63- 1108.32 ng/mL). This method was adapted for therapeutic drug monitoring.
      PubDate: 2017-11-17T06:00:20.964149-05:
      DOI: 10.1002/bmc.4140
  • Development and validation of a high-performance liquid chromatography
           method for determination of lisinopril in human plasma by magnetic
           solid-phase extraction and pre-column derivatization
    • Authors: Noushin Rastkari; Reza Ahmadkhaniha
      Abstract: A sensitive, reliable and simple HPLC method was developed for the determination of lisinopril in human plasma. The method consists of extraction and clean-up steps based on magnetic solid-phase extraction and pre-column derivatization with a fluorescent reagent. The mobile phase consisted of a mixture of methanol–sodium dihydrogen phosphate (pH 3.0; 0.005 m; 75:25, v/v). The flow rate was set at 0.7 mL/min. Fluorescence detection was performed at 470nm excitation and 530nm emission wavelengths. Total chromatography run time was 5 min. The average extraction recovery of lisinopril and fluvoxamine (internal standard) was ≥82.8%. The limits of detection and quantification were determined as 1 and 3 ng/mL respectively. The method exhibited a linear calibration line over the concentration range of 3–1000 ng/mL with coefficient of determination (r2) of ≥0.98. The within-run and between-run precisions were satisfactory with values of CV of 1.8–12.8% (accuracy from 99.2 to 94.7%) and 2.4–13.7% (accuracy from 99.5 to 92.2%), respectively. These developments led to considerable improvement in method sensitivity and reliability. The method was validated according to the US Food and Drug Administration guidelines. Therefore, it can be considered as a suitable method for determination of lisinopril in plasma samples.
      PubDate: 2017-11-16T23:40:35.341228-05:
      DOI: 10.1002/bmc.4120
  • Simultaneous determination of tilianin and its metabolites in mice using
           ultra-high-performance liquid chromatography with tandem mass spectrometry
           and its application to a pharmacokinetic study
    • Authors: Liping Wang; Qingwei Chen, Lijun Zhu, Xuejun Zeng, Qiang Li, Ming Hu, Xinchun Wang, Zhongqiu Liu
      Abstract: Tilianin is an active flavonoid glycoside found in many medical plants. Data are lacking regarding its pharmacokinetics and disposition in vivo. The objective of this study was to develop a sensitive, reliable, and validated ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method to simultaneously quantify tilianin and its main metabolites and to determine its pharmacokinetics in wild-type and breast cancer resistance protein knockout (Bcrp1-/-) FVB mice. Chromatographic separation was accomplished on a C18 column by utilizing acetonitrile and 0.5 mM ammonium acetate as the mobile phase. Mass spectrometric detection was performed using electrospray ionization in both positive and negative modes. The results showed that the precision, accuracy, and recovery, as well as the stability of tilianin and its metabolites in mouse plasma were all within acceptable limits. Acacetin-7-glucuronide (Aca-7-G) and acacetin-7-sulfate (Aca-7-S) were the major metabolites of tilianin in mouse plasma. Moreover, systemic exposure of Aca-7-S was significantly higher in Bcrp1 (-/-) FVB mice compared with wild-type FVB mice. In conclusion, the fully validated UHPLC-MS/MS method was sensitive, reliable, and successfully applied to assess the pharmacokinetics of tilianin in wild-type and Bcrp1 (-/-) FVB mice. BCRP had a significant impact on the elimination of the sulfated metabolite of tilianin in vivo.
      PubDate: 2017-11-16T08:35:19.851686-05:
      DOI: 10.1002/bmc.4139
  • Determination of tubuloside B by LC–MS/MS and its application to a
           pharmacokinetic study in rats
    • Authors: Shenbao Yang; Ruiying Qu, Peilu Sun, Shan Xiong, Siyi Yan, Zhipeng Deng
      Abstract: Tubuloside B, a novel neuroprotective phenylethanoid, is a major active constituent of Cistanche tubulosa and Cistanche deserticola. A specific and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantification of tubuloside B in rat plasma. Sample preparation was conducted through a protein-precipitation extraction with methanol using tubuloside A as internal standard (IS). Chromatographic separation was achieved by using a Capcell Pak C18 column (2.0 mm × 50 mm, 5 μm) with a mobile phase of methanol-10 mM ammonium acetate buffer (70:30, v/v) in an isocratic elution way. Mass spectrometry (MS) analysis was performed in negative ionization mode with selection reaction monitoring (SRM) transitions at m/z 665.1 160.9 for tubuloside B, and m/z 827.1 160.9 for IS. Calibration curves were linear over the ranges of 1.64–1640 ng/mL for plasma samples samples (R2> 0.990). The lower limit of quantification (LLOQ) was 1.64 ng/mL. The intra-day and inter-day accuracy was between 92.3% and 113.0% with the RSD less than 9.23% at all LLOQ and QC levels. Finally, this method was successfully applied in the pharmacokinetics study of tubuloside B after intravenous administration.
      PubDate: 2017-11-16T08:21:50.264101-05:
      DOI: 10.1002/bmc.4138
  • Sample Preparation for Large Scale Bioanalytical Studies Based on Liquid
           Chromatographic Techniques
    • Authors: Andrei Medvedovici; Elena Bacalum, Victor David
      Abstract: Quality of the analytical data obtained for large-scale and long term bioanalytical studies based on liquid chromatography depends on a number of experimental factors including the choice of sample preparation method. This review discusses this tedious part of bioanalytical studies, applied to large scale samples and using liquid chromatography coupled with different detector types as core analytical technique. The main sample preparation methods included in this paper are protein precipitation, liquid-liquid extraction, solid-phase extraction, derivatization, and their versions. They are discussed by analytical performances, fields of applications, advantages and disadvantages. The cited literature covers mainly the analytical achievements during the last decade, although several previous papers became more valuable in time and they are included in this review.
      PubDate: 2017-11-16T07:15:20.386527-05:
      DOI: 10.1002/bmc.4137
  • Issue information
    • Abstract: No abstract is available for this article.
      PubDate: 2017-11-16T01:23:59.862338-05:
      DOI: 10.1002/bmc.3846
  • A novel fast method for aqueous derivatization of THC, OH-THC and THC-COOH
           in human whole blood and urine samples for routine forensic analyses.
    • Authors: Fabio Stefanelli; Federica Giorgia Pesci, Mario Giusiani, Silvio Chericoni
      Abstract: A novel aqueous in situ derivatization procedure with propyl chloroformate (PCF) for the simultaneous, quantitative analysis of Δ9-tetrahydrocannabinol (THC), 11-hydroxy-Δ9-tetrahydrocannabinol (OH-THC) and 11-nor-Δ9-tetrahydrocannabinol-carboxylic acid (THC-COOH) in human blood and urine is proposed.Unlike current methods based on the silylating agent (BSTFA) added in an anhydrous environment, this new proposed method allows to add the derivatizing agent (propyl chloroformate, PCF) directly to the deproteinized blood and recover the derivatives by liquid-liquid extraction. This novel method can be also used for hydrolyzed urine samples, which is faster than the traditional method involving a derivatization with trimethyloxonium tetrafluoroborate (TMO).The analytes are separated, detected and quantified by gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring mode (SIM). The method was validated in terms of selectivity, capacity of identification, limits of detection (LOD) and quantification (LOQ), carryover, linearity, intra-assay precision, inter-assay precision and accuracy.The limits of detection (LOD) and quantification (LOQ) in hydrolyzed urine were 0.5 ng/mL and 1.3 ng/mL for THC and 1.2 ng/mL and 2.6 ng/mL for THC-COOH, respectively. In blood, the LOD and LOQ were 0.2 ng/mL and 0.5 ng/mL for THC, 0.2 ng/mL and 0.6 ng/mL for OH-THC, 0.9 ng/mL and 2.4 ng/mL for THC-COOH, respectively.This method was applied to thirty-five urine samples and fifty blood samples resulting to be equivalent to the current ones with the advantage of a more simple and faster sample processing time. We believe it will be a more convenient option for the routine analysis of cannabinoids in toxicological and forensic laboratories.
      PubDate: 2017-11-14T08:16:36.089091-05:
      DOI: 10.1002/bmc.4136
  • Analysis and Measurement of Serotonin
    • Authors: András Seitz; Stelvio M. Bandiera
      Abstract: Serotonin, also known as 5-hydroxytryptamine, is an important signaling molecule in the central and peripheral nervous systems of humans. Acting through several receptor types, it helps regulate the normal functioning of the gastrointestinal tract, cardiovascular system and brain. Serotonin signaling has also been implicated in the etiology of several diseases, including depression, anxiety disorders, hypertension and irritable bowel syndrome. The present review focuses on the chemical analysis of serotonin in biological fluids and biomatrices and traces the development and application of early methods based on UV absorbance or fluorescence to more widely-used current methods such as high-performance liquid chromatography coupled to mass spectrometry. A brief summary of the biochemistry, metabolism and physiological roles of serotonin is also presented.
      PubDate: 2017-11-14T07:55:20.547073-05:
      DOI: 10.1002/bmc.4135
  • Analytical approach, dissipation pattern, and risk assessment of pesticide
           residue in green leafy vegetables: A comprehensive review
    • Authors: Waziha Farha; A.M. Abd El-Aty, Md. Musfiqur Rahman, Ji Hoon Jeong, Ho-Chul Shin, Jing Wang, Sung Shik Shin, Jae-Han Shim
      Abstract: The category of “leafy vegetables” comprises a wide range of plants, including cabbage, lettuce, leeks, spinach, Swiss chard, and kale, and it forms a significant component of the human diet. Typically, leafy vegetables are low in calories and fat, are great sources of vitamins, protein, dietary fibre, minerals (including iron, calcium, and nitrates), and are rich in phytochemicals. To counter the impact of pests on vegetables, a broad variety of pesticides is used. Because of their large surface areas, leafy vegetables are expected to have high residual pesticide levels. As such, a sound analytical approach was necessary to detect and quantify residue levels that are equal to or lower than the maximum residue limits (MRL), thus rendering the products safe for consumption. Overall, leafy vegetables consumed raw (after a tap water wash only), boiled, or steamed contribute 2% of total vegetable consumption globally, and they might have a comparatively greater influence on health than that of cereal ingestion. Consequently, in this review paper, we highlight the importance of leafy vegetables, the pesticides that are commonly used on them, and various analytical techniques, including sample preparation, extraction, clean-up, and final detection. The effects on dissipation patterns, pre-harvest residue limits, and safety/risks imposed by various pesticides are also reviewed and discussed. In conclusion, environmentally-friendly extraction methods coupled with high throughput techniques with greater reproducibility and lower uncertainty are needed for quantifying residues in leafy vegetables at very low concentrations. Commercial and household food preparation, such as washing, peeling, blanching, and cooking are effective in removing most of the pesticide residues that are loosely attached on vegetables.
      PubDate: 2017-11-14T01:10:23.435941-05:
      DOI: 10.1002/bmc.4134
  • Chromatographic analysis of VOC patterns in exhaled breath from smokers
           and nonsmokers
    • Authors: Simonetta Capone; Maria Tufariello, Angiola Forleo, Valentina Longo, Lucia Giampietruzzi, Antonio Vincenzo Radogna, Flavio Casino, Pietro Siciliano
      Abstract: Cigarette smoking harms nearly every organ of the body and causes many diseases. The analysis of exhaled breath for exogenous and endogenous Volatile Organic Compounds (VOCs) can provide fundamental information on active smoking and insight into the health damage that smoke is creating. Various exhaled Volatile Organic Compounds (VOCs) have been reported as typical of smoking habit and recent tobacco consumption, but to date, no eligible biomarkers have been identified. Aiming to identify such potential biomarkers, in this pilot study we analysed the chemical patterns of exhaled breath from 26 volunteers divided in groups of nonsmokers and subgroups of smokers sampled at different periods of withdrawal from smoking. Solid Phase MicroExtraction technique (SPME) and Gas Chromatography/Mass Spectrometry (GC/MS) method were applied.Many breath VOCs were identified and quantified in very low concentrations (ppbv range), but only a few (toluene, pyridine, pyrrole, benzene, 2-butanone, 2-pentanone, 1-methyldecyclamine) were found to be statistically significant variables by Mann-Whitney test. In our analysis, we didn’t consider the predictive power of individual VOCs, as well as the criterion of uniqueness for biomarkers suggests, but on the contrary, we used the patterns of the only statistically significant compounds. Probit prediction model based on statistical relevant VOCs-patterns showed that assessment of smoking status is heavily time dependent; it's possible recognise with high specificity and sensitivity smokers after a short-term exposure to tobacco (i.e. after 1 hour of smoking abstinence), whereas smokers after a long-term exposure to tobacco (i.e. after a night out of smoking) are more like non-smokers.
      PubDate: 2017-11-13T08:35:20.597493-05:
      DOI: 10.1002/bmc.4132
  • Method development for Quantification of Quizartinib in Rat Plasma by
           Liquid Chromatography/Tandem Mass Spectrometry for pharmacokinetic
    • Authors: Essam Ezzelddin; Muzaffar Iqbal, Gamal Mostafa, Khalid A. Al-Rashood, Toqa El nahhas
      Abstract: Quizartinib is a highly potent inhibitor of the fms-like tyrosine kinase receptor, which is one of the most commonly mutated genes in acute myeloid leukemia (AML). Quizartinib has shown a significant antileukemic clinical influence among relapsed/refractory acute AML patients. This study aimed at developing and validating an analytical method for the measurement of quizartinib in rat plasma using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The method was validated according to FDA guidelines, and the results obtained in this work met the set criteria. Liquid–liquid extraction was used and chromatographic separation was achieved on a BEHTM C18 column. Detection of quizartinib was achieved in the multiple reaction monitoring mode using positive-ion mode electrospray ionization. The MS/MS ion transitions at mass-to-charge ratios (m/z) of 561.129/114.09 and 441.16/84.03 were monitored for quizartinib and ibrutinib, respectively. The linear detection range was 2–1000 ng/mL (r> 0.998), with intraand inter-day assay precisions equal to or less than 13.07% and 13.17%, respectively. This rapid, simple, and sensitive method was validated and successfully applied to the pharmacokinetic study of quizartinib in rat samples.
      PubDate: 2017-11-13T08:15:27.53241-05:0
      DOI: 10.1002/bmc.4131
  • Combined Metabolomic and Correlation Networks Analyses Reveal Fumarase
           Insufficiency Altered Amino Acids Metabolism
    • Authors: Entai Hou; Xian Li, Zerong Liu, Fuchang Zhang, Zhongmin Tian
      Abstract: Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. Fumarase insufficiencies were associated with increased level of fumarate and decreased level of malate and exacerbated salt-induced hypertension. To gain insights into the metabolism profiles that induced by fumarase insufficiency and identify key regulatory metabolites, we applied a GC–MS based metabolomics platform coupled with a network approach to analyze fumarase insufficient HUVEC cells and negative controls. A total of 24 altered metabolites involved in 7 metabolic pathways were identified as significantly altered, and enriched for the biological module of amino acids metabolism. In addition, Pearson correlation network analysis revealed that fumaric acid, L-malic acid, L-aspartic acid, glycine and L-glutamic acid were hub metabolites according to Pagerank based on their three centrality indices. ALT and GDH activities increased significantly in fumarase deficiency HUVEC cells. These results confirmed that fumarase insufficiency altered amino acid metabolism. The combination of metabolomics and network methods would provide another perspective on expounding the molecular mechanism at metabolomics level.
      PubDate: 2017-11-11T10:20:33.490875-05:
      DOI: 10.1002/bmc.4133
  • Simultaneous determination and pharmacokinetic study of giraldoid A,
           giraldoid B in rat plasma after oral administration of Daphne giraldii
           Nitsche extracts by LC-MS/MS
    • Authors: Huyiligeqi; Xiaoxv Dong, Jing Fu, Sali Cao, Chunjing Yang, Longtai You, Zhongyi Zhang, Jian Ni
      Abstract: A simple sensitive LC-MS/MS method has been developed for the simultaneous determination of giraldoid A and giraldoid B in rat plasma. The method was applied to the pharmacokinetics studies of the two compounds from Daphne giraldii Nitsche. Chromatographic separation was accomplished on an ACQUITY UPLC™ BEH C18 column (100 × 2.1 mm, 1.7 mm) by gradient elution with a flow rate of 0.2 mL min-1. The method was linear over the concentration range of 1.0-1000 ng mL-1, and the lower limit of quantification were 1.04 ± 0.10, 1.04 ± 0.09 ng mL-1, respectively. The intra- and inter-day precisions (RSD) were less than 10.14 and 9.96 %. The extraction recovery of the analytes was acceptable. Stability studies demonstrated that the two compounds were stable in the preparation and analytical process. The maximum plasma concentration (Cmax) was 687.78 ± 243.62 ng mL-1 for giraldoid A and 952.38 ± 131.99 ng mL-1 for giraldoid B, respectively. The time to reach the maximum plasma concentration (Tmax) was 0.50 ± 0.37 h for giraldoid A and 0.50 ± 0.66 h for giraldoid B, respectively. The validated method was successfully applied to investigate the concentration-time profiles of giraldoid A and giraldoid B.
      PubDate: 2017-11-07T00:00:45.361948-05:
      DOI: 10.1002/bmc.4129
  • Simultaneous determination and tissue distribution studies of four
           phenolic acids in rat tissue by UFLC-MS/MS after intravenous
           administration of salvianolic acid for injection
    • Authors: Shuang Li; Xiuman Xie, Dongxiang Li, Zhiguo Yu, Ling Tong, Yunli Zhao
      Abstract: A rapid, simple and sensitive ultra-fast liquid chromatography tandem mass spectrometric method was developed and validated for simultaneous determination and tissue distribution studies of rosmarinic acid, salvianolic acid D, lithospermic acid and salvianolic acid B in rats after intravenous administration of salvianolic acid for injection. The tissue homogenate samples were pretreated by protein precipitation with pre-cooled acetonitrile. Chromatographic separation was achieved on a Waters Cortecs UPLC C18 column (1.6 μm, 2.1 × 100 mm) with a mobile phase composed of 0.1% formic acid-water and 0.1% formic acid-acetonitrile. Analytes were detected by electrospray ionization mass spectrometry and quantitated using multiple reaction monitoring. The method was fully validated. The calibration curves for the four phenolic acids were linear in the given concentration ranges. The precision (relative standard deviation) in the measurement of quality control samples were less than 10% and the accuracy (relative error) were in the range of 0.28%-11.22%. The reliable method was successfully applied to the tissue distribution studies of the four phenolic acids. The results showed that rosmarinic acid, salvianolic acid D, lithospermic acid and salvianolic acid B were rapidly distributed in tissues with the major amount found in kidney, and little amount crossed the blood-brain barrier. The developed method and the results can provide a basis for further studies.
      PubDate: 2017-11-06T02:51:36.395902-05:
      DOI: 10.1002/bmc.4128
  • Pharmacokinetics of Pidotimod in Broiler Chickens by UHPLC-MS/MS after
           Oral and Intravenous Administration
    • Authors: Ruili Zhang; Mei Qiu, Li Zhao, Liangliang Cui, Chunyuan Wang, Jiajia Zhu, Zhihui Hao
      Abstract: Pidotimod is widely used in children as an immune promoter but it has not been fully evaluated in animals. Pharmacokinetics of pidotimod and its oral bioavailability have not been described in broiler chickens. We developed a simple and sensitive UHPLC-MS/MS assay for rapid determination of pidotimod levels in chicken blood. Recoveries were nearly 100% and the coefficients of accuracy and precision were minimal. Healthy broiler chickens were given 10 mg/kg pidotimod either orally or intravenously. The oral pidotimod was rapidly absorbed [time of reaching maximum concentration (tmax) 1.25h] and rapidly eliminated (the mean residence times was 3.2h) A noncompartmental analysis of the intravenous route indicated a mean plasma clearance of 2.2 L· (h·kg)-1 with an estimated mean volume of distribution at steady-state of 12.69 L/kg. Bioavailability of pidotimod after oral dosing was 27%.
      PubDate: 2017-11-06T02:51:34.271824-05:
      DOI: 10.1002/bmc.4130
  • Proteomics analysis of altered proteins in kidney of mice with
           aristolochic acid nephropathy using the fluorogenic derivatization-liquid
           chromatography-tandem mass spectrometry method
    • Authors: Chia-En Lin; Wen-Shin Chang, Jen-Ai Lee, Ting-Ya Chang, Yu-Shen Huang, Yoshiro Hirasaki, Hung-Shing Chen, Kazuhiro Imai, Shih-Ming Chen
      Abstract: Aristolochic acid (AA) causes interstitial renal fibrosis, which called aristolochic acid nephropathy (AAN). There is no specific indicator for diagnosing AAN, so this study was to investigate the biomarkers for AAN using a proteomics method. The C3H/He female mice were given ad libitum AA-distilled water (0.5 mg/kg/day) and distilled water for 56 days in the AA and normal groups, respectively. The AA-induced proteins in the kidney were investigated using a proteomics study, including fluorogenic derivatization with 7-chloro-N-[2-(dimethylamino)ethyl]-2,1,3- benzoxadiazole-4-sulfonamide (DAABD-Cl), and followed by high performance liquid chromatography analysis and liquid chromatography tandem mass spectrometry (FD-LC-MS/MS) with a MASCOT database searching system. There were two altered proteins, thrombospondin type 1 (TSP1) and G protein-coupled receptor 87 (GPR87), in the kidney of AA-group mice on day 56. GPR87, tumorigenesis-related protein, was newly reported in the current study. The renal interstitial fibrosis was certainly induced in the AA-group mice under the observation of histological examination. Based on the results of histological examination and proteomics study, this model might be applied to AAN studies in the future. TSP1 might be a novel biomarker for AAN, and the further role of GPR87 leading to AA-induced tumorigenesis should be researched in future studies.
      PubDate: 2017-10-31T13:00:20.439785-05:
      DOI: 10.1002/bmc.4127
  • A sensitive LC-MS/MS method for simultaneous quantification of geniposide
           and its active metabolite genipin in rat plasma and its application to a
           pharmacokinetic study
    • Authors: Fuguo Shi; Hong Pan, Yi Li, Linyan Huang, Qin Wu, Yuanfu Lu
      Abstract: Genipin (GP), an active metabolite of geniposide (GE), exhibited more potent pharmacological effects than its parent compound. In this paper, a sensitive LC-MS/MS method was developed and fully validated for the simultaneous determination of GE and GP in rat plasma. We found GP degraded rapidly in rat plasma at room temperature as a result of the irreversible binding with the endogenous nucleophiles in plasma. GP is stable when the samples pH is less than or equal to 4.0. The degradation of GP in rat plasma was well prevented by immediate addition of 5% glacial acetic acid to the freshly collected plasma. The detection was performed on a tandem mass spectrometer coupled with electrospray ionization source in negative mode. Quantification was conducted by multiple reaction monitoring of the transitions of at [M+CH3COO]- m/z 447.3225.3 for GE, and at [M-H]- m/z 225.2123.1 for GP. The method exhibited high sensitivity (LLOQ of 1 ng/mL for GE and 0.2 ng/ml for GP) by selecting the acetate adduct ions as the precursor ion for GE. The robust developed method was successfully applied to a pharmacokinetic study in rats after oral administration of GE.
      PubDate: 2017-10-31T12:30:23.344027-05:
      DOI: 10.1002/bmc.4126
  • Simultaneous separation and analysis of camptothecin alkaloids in real
           samples by large volume sample stacking in capillary electrophoresis
    • Authors: Meng Chen; Yayun Huang, Liying Xu, Hongfen Zhang, Guangbin Zhang, Anjia Chen
      Abstract: Large-volume Sample Stacking (LVSS) is commonly used as an effective on-line preconcentration method in capillary zone electrophoresis (CZE). In this paper, the method LVSS combined with CZE has been proposed to analysis the camptothecin alkaloids. Optimum separation can be achieved in conditions as following: pH 9.0, 25 mM borate buffer containing 20 mM Sulfobutylether-β-Cyclod-extrin (SBE-β-CD) and 20 mM ionic liquid [EMIM] [L-Lac] (IL), the applied voltage was 20 kV and the capillary temperature was 25°C. The LVSS was optimized as hydrodynamic injection 4 s at 5.0 psi and the polarity switching time was 0.17 min. Under the above conditions, the analytes could be separated completely in less than 20 min and the detector response had been increased compared with conventional hydrodynamic injection. The limit of detection were between 0.20 and 0.78 μg/L. A good linearity could be obtained with correlation coefficients from 0.9991 to 0.9997. The recoveries ranged from 97.72 to 103.2% and the results demonstrated excellent accuracy. In terms of the migration time and peak area, the experiment was reproducible. And the experimental results indicated that baseline separation can be obtained and this method is suitable for the quantitative determination of camptothecin alkaloids in real samples.
      PubDate: 2017-10-31T11:40:22.293711-05:
      DOI: 10.1002/bmc.4125
  • A sensitive HPLC-MS/MS method for the simultaneous determination of
           Anemoside B4, Anemoside A3 and 23-hydroxybetulinic acid: application to
           the pharmacokinetics and liver distribution of Pulsatilla chinensis
    • Authors: Xiaozhen Guo; Yang Xie, Shan Lian, Zhixiong Li, Yu Gao, Zhou Xu, Pei Hu, Mingcang Chen, Zhaolin Sun, Xiaoting Tian, Chenggang Huang
      Abstract: Pulsatilla chinensis saponins, the major active components in the herb, have drawn great attention as potential hepatitis B virus infection and hepatoma treatments. Here, a sensitive and accurate HPLC-MS/MS method was established for simultaneous determination of three saponins, Anemoside B4, Anemoside A3 and 23-hydroxybetulinic acid, in rat plasma and liver, and fully validated. The method was successfully applied to the pharmacokinetics and liver distribution study of Pulsatilla chinensis saponins. Consequently, 23-hydroxybetulinic acid, with an extremely low content in the P. chinensis saponins, exhibited the highest exposure in the liver and in sites before and after hepatic disposition, namely, in the portal vein plasma and systemic plasma, followed by Anemoside B4, which was of the highest content in the herb, whereas Anemoside A3 displayed quite limited exposure. The hepatic first-pass effects were 71% for 23-hydroxybetulinic acid, 27% for Anemoside B4 and 37% for Anemoside A3, corresponding to their different extent of liver distribution. To our knowledge, this is the first investigation on the liver first-pass effect and distribution of Pulsatilla chinensis saponins to date. These results also provide valuable information for the understanding of the pharmacological effect of Pulsatilla chinensis saponins on liver diseases.
      PubDate: 2017-10-27T16:20:27.04103-05:0
      DOI: 10.1002/bmc.4124
  • Preparation and evaluation of a chiral HPLC stationary phase based on cone
           calix[4]arene functionalized at the upper rim with L-alanine units
    • Authors: Sadegh Yaghoubnejad; Kourosh Tabar Heydar, Seyyed Hamid Ahmadi, Reza Zadmard
      Abstract: Here we report a new chiral stationary phase (CSP) immobilized on silica gel based on cone calix[4]arene functionalized at the upper rim with two L-alanine units as new chiral selector that has been used in high performance liquid chromatography. The CSP was prepared by covalently bonding the allyl groups at the lower rim of calix[4]arene to silica gel by thiol-ene click chemistry reaction. Elemental analysis of the CSP showed that 120 μmol of chiral selector bonded per gram of silica gel. 1-Hexene was used for end-capping of unreacted mercapto groups on silica gel. Since the CSP is chemicaly bonded to the silica, it can be used in the normal-phase mode, reversed-phase mode and with halogenated solvents mobile phases, if desired. The chromatographic performance of the CSP was evaluated in the enantioseparation of the 3,5-dinitrobenzoyl (DNB) derivatives of some amino acids, diclofop-methyl, and DL-mandelic acid.
      PubDate: 2017-10-23T14:25:20.967583-05:
      DOI: 10.1002/bmc.4122
  • Simultaneous Determination of Usnic, Diffractaic, Evernic and Barbatic
           Acids in Rat Plasma by Ultra High Performance Liquid
           Chromatography-Quadrupole Exactive Orbitrap Mass Spectrometry and Its
           Application to Pharmacokinetic Studies
    • Authors: Hanxue Wang; Tao Yang, Xuemei Cheng, Sukfan Kwong, Chenghai Liu, Rui An, Guowen Li, Xinhong Wang, Changhong Wang
      Abstract: Usnea longissima Ach. (Usnea) has been used in pharmaceuticals, food, cosmetics. Evernic acid (EA), barbatic acid (BA), diffractaic acid (DA), and usnic acid (UA) are the most typical ingredients in U. longissima and exert a wide variety of biological functions. The study aim to develop a sensitive method for simultaneous analysis of EA, BA, DA, and UA in rat plasma and applied to pharmacokinetic studies after consumption of UA and ethanol extract from U. longissima (UE). The samples were separated on BEH C18 column by gradient elution with 0.5% formic acid in water and in methanol. The relative molecular masses of analytes were obtained in full scan range from 50.0 to 750.0 m/z under negative ionization mode by UPLC-Q-Exactive Orbitrap MS. All validation parameters, such as lower limit of quantitation, linearity, specificity, precision, accuracy, extraction recovery, matrix effect and stability, within acceptable ranges and the method was appropriate for biological specimen analysis. The pharmacokinetics results indicated that the absolute bioavailability of UA after oral administration of UA and UE reaches 69.2% and 146.9%, respectively. Comparing to UA in UE, the relative bioavailability of DA, BA and EA reaches 103.7%, 10.4%, and 0.7% after oral administration of UE.
      PubDate: 2017-10-21T00:20:23.851016-05:
      DOI: 10.1002/bmc.4123
  • Identification of absorbed constituents and in vivo metabolites in rats
           after oral administration of Physalisalkekengi var. franchetii by
           ultrahigh-pressure liquid chromatography quadrupole time-of-flight mass
    • Authors: Xinchi Feng; Xiaoguang Huo, Hongxia Liu, Liwei Chai, Liqin Ding, Feng Qiu
      Abstract: The calyces of Physalisalkekengi var. franchetii (Chinese Lantern, JDL) are well-known traditional Chinese medicine owing to its various therapeutic effects. However, the bioactive constituents responsible for the pharmacological effects of JDL and their metabolites in vivo are still unclear to date. In this paper, an ultrahigh-pressure liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/Q–TOF–MS/MS) method was established to identify absorbed constituents and in vivo metabolites in rat biological fluids after oral administration of JDL. Based on the proposed strategy, 33 compounds were observed in dosed rat biosamples. 12 of 33 compounds were indicated as prototype components of JDL, and 21 compounds were predicted to be metabolites of JDL. Finally, the metabolic pathways were proposed, which were the glucuronidation, sulfation, methylation and dehydroxylation for flavonoids constituents and sulfonation and hydroxylation for physalins consitituents. This is the first systematic study on the absorbed constituents and metabolic profiling of JDL and will provide a useful template for screening and characterizing the ingredients and metabolites of traditional Chinese medicine.
      PubDate: 2017-10-20T22:35:34.089163-05:
      DOI: 10.1002/bmc.4121
  • Retention behavior of flavonoids on Immobilized Artificial Membrane
           Chromatography and correlation with cell- based permeability
    • Authors: Fotios Tsopelas; Maria Tsagkrasouli, Pavlos Poursanidis, Maria Pitsaki, George Vasios, Panagiotis Danias, Irene Panderi, Anna Tsantili- Kakoulidou, Constantinos Giaginis
      Abstract: The aim of the study was to investigate IAM retention mechanism for a set of flavonoids and to evaluate the potential of IAM chromatography to model Caco-2 permeability. For this purpose, the retention behavior of 41 flavonoid analogues on two immobilized artificial membrane (IAM) stationary phases, IAM.PC.MG and IAM.PC.DD2, was investigated. Correlations between retention factors, logkw(IAM) and octanol- water partitioning (logP) were established and the role of hydroxyl groups of flavonoids to the underlying retention mechanism was explored. IAM retention and logP values were used to establish sound linear models with Caco-2 permeability (logPapp) taken from the literature. Both stepwise regression and multivariate analysis confirmed the contribution of hydrogen bond descriptors, as additional parameters in the either logkw(IAM) or logP models. Retention factors on both IAM stationary phases showed comparable performance with n-octanol- water partitioning towards Caco-2 permeability.
      PubDate: 2017-10-18T03:25:21.716949-05:
      DOI: 10.1002/bmc.4108
  • Characteristic components profiling and identification of different
           Uncaria species based on high performance liquid chromatography-photodiode
           array detector tandem ion trap and time of flight mass spectrometer
           coupled with rDNA ITS sequence
    • Authors: Bingqiang Zhao; Yanjun Huang, Qiulan Chen, Qizhao Chen, Hui Miao, Shuang Zhu, Changqing Zeng
      Abstract: The Uncaria is a multi-source herb and its species identification has become a bottleneck in quality control. To study the identification method of different Uncaria species herbs through HPLC-MS coupled with rDNA Internal Transcribed Spacer (rDNA ITS) sequence, both plant morphological traits and molecular identification were used to determine the species of every collected Uncaria herbs. The genetic analysis of different Uncaria species was performed by using their rDNA ITS sequence as a molecular marker. Meanwhile, the phylogenetic relationships of 22 samples from six Uncaria species were divided and classified clearly. By optimizing the chromatographic conditions, a practical HPLC method to differentiate various varieties of Uncaria herbs was set up based on a set of characteristic components across each species. A high-performance liquid chromatography-photodiode array detector tandem ion trap and time of flight mass spectrometer (LCMS-IT-TOF) technique combined with reference substances was utilized to derive 21 characteristic compounds containing six groups of six Uncaria species in China. Thus, this study provides a feasible method to solve the current problem of confusion in Uncaria species, and makes a significant step forward in the appropriate clinical use, in-depth research, and further utilization of different Uncaria species.
      PubDate: 2017-10-16T00:51:02.909148-05:
      DOI: 10.1002/bmc.4119
  • Determination of Thiocyanate as a Biomarker of Tobacco Smoke Constituents
           in Selected Biological Materials of Human Origin
    • Authors: Sylwia Narkowicz; Ewa Jaszczak, Żaneta Polkowska, Bogumiła Kiełbratowska, Alicja Kotłowska, Jacek Namieśnik
      Abstract: In order to protect human health, it is necessary to biomonitor toxic substances originating from tobacco smoke in biological materials sampled from the persons with different exposures to tobacco smoke constituents. Thiocyanate anion is a biomarker of exposure to tobacco smoke components which is characterized by a relatively long half-life in the human body, i.e. 6 days. In this work, we present the results of thiocyanate determinations performed on the samples of placenta, meconium, saliva, breast milk, sweat and blood. The placenta samples were subjected to accelerated solvent extraction with water. The thiocyanate concentrations were determined by using ion chromatography. The analyzed biological materials were compared with regard to their applicability for biomonitoring toxic substances originating from tobacco smoke. The highest mean concentrations of thiocyanate were observed in the samples of biological materials collected from active smokers.
      PubDate: 2017-10-13T04:26:23.81266-05:0
      DOI: 10.1002/bmc.4111
  • Chemical interaction between Lilium brownii and Rhizoma Anemarrhenae, the
           herbal constituents of Baihe Zhimu decoction, by liquid chromatography
           coupled to hybrid triple quadrupole linear ion trap mass spectrometer
    • Authors: Bo Yang; Zhirui Liu, Qian Wang, Peiyuan Xia
      Abstract: During the course of decoction, the components of herbal formula interact with each other, such that chemical extraction characteristics are altered. The crude drugs, Lilium brownii (Baihe) and Rhizoma Anemarrhenae (Zhimu), are the herbal constituents of Baihe Zhimu decoction, a traditional herbal formula. To investigate the chemical interaction between Baihe and Zhimu when decocting together, eight marker components in Baihe Zhimu decoction were simultaneously characterized and quantified in one run by a hybrid triple quadrupole linear ion trap mass spectrometer in the multiple reactions monitoring-information dependent acquisition-enhanced product ion (MRM-IDA-EPI) mode. The results showed that Zhimu significantly suppressed the extraction of phenolic glycosides (the components from Baihe) when co-decocting, and Baihe clearly suppressed the extraction of xanthones and steroidal saponins (the components from Zhimu). Overall, the presently developed method would be a preferred candidate for the investigation of the chemical interaction between herbal medicines.
      PubDate: 2017-10-13T04:26:03.434539-05:
      DOI: 10.1002/bmc.4118
  • Toxicokinetics of strychnine and brucine after the oral administration of
           Biqi capsule to rats by RRLC-MS/MS
    • Authors: Hao Zheng; Zhe Wang, Wenwei Liu, Hongtao Jin, Jinlan Zhang
      Abstract: Biqi capsule is a well-known traditional Chinese medicine (TCM) formula that has been widely applied for the clinical treatment of such diseases as rheumatoid arthritis, scapulohumeral periarthritis, and cervical spondylopathy. However, there is concern regarding the toxicity of Biqi capsule due to its active ingredients, strychnine and brucine. To investigate the toxicokinetics of strychnine and brucine after the oral administration of Biqi capsule to rats, a sensitive and simple rapid-resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS) method was developed to determine the levels of strychnine and brucine in rat plasma. Chromatographic separation was performed on a CAPCELL PAK C18 MG II (3.0 μm, 2.0×35 mm) column by gradient elution with acetonitrile and 0.2% formic acid as the mobile phase. The method was validated over the range of 0.25 to 250 ng/mL for strychnine and 0.025 to 25 ng/mL for brucine. The intra- and inter-day accuracies of strychnine and brucine in rat plasma were 100.3%-106.6% and 90.75%-106.1% respectively, and the precisions were within 14.2%. The established method was successfully applied to the toxicokinetic study of strychnine and brucine after single and multiple oral administration of Biqi capsule to male and female rats at 0.4-, 0.8-, and 1.6-g/kg doses. The results showed different toxicokinetic characteristics in the different groups.
      PubDate: 2017-10-13T04:25:51.779297-05:
      DOI: 10.1002/bmc.4117
  • Comparison of Plasma Pharmacokinetics of Tanreqing Solution between
           Intratracheal Aerosolization and Intravenous Injection in Rats
    • Authors: Cui Li; Siyu Liu, Gan Luo, Guohua Wang, Baoxian Zhang, Qixia Nie
      Abstract: A rapid ultra high performance liquid chromatography tandem mass spectrometry method was developed for the simultaneous analysis of baicalin, oroxylin A-7-O-β-D-glucoronide and chlorogenic acid in rats plasma, and it was applied to comparison of pharmacokinetics of Tanreqing solution between intratracheal aerosolization and intravenous injection. Results of the analytical method validation assay showed high sensitivity, accuracy and suitable recovery. Results of pharmacokinetics showed a similar decline phase for baicalin, oroxylin A-7-O-β-D-glucoronide and chlorogenic acid in two different delivery routes. The T1/2 (h) of intratracheal aerosolization and intravenous injection are 0.90 and 1.22 for baicalin, 0.47 and 0.17 for oroxylin A-7-O-β-D-glucoronide, 0.22 and 0.13 for chlorogenic acid, and implies that compounds was retained in the lung for a relatively short time. This study was the first to provide important pharmacokinetics information for traditional Chinese medicine delivery to the lung.
      PubDate: 2017-10-13T04:25:45.229735-05:
      DOI: 10.1002/bmc.4116
  • Development of an LC-MS/MS method for quantification of two isomeric
           phenylpropenes and the application to pharmacokinetic studies in rats
    • Authors: Qiong Yang; Zhipeng Deng, Fang Zhang, Peilu Sun, Jun Li, Wanjin Zheng
      Abstract: Isomers β-asarone and α-asarone have recently demonstrated differential pharmacological activities. Here, we report an LC-MS/MS method developed using acetonitrile to extract two isomeric phenylpropenes from rat plasma. Separation was achieved using a XDB-C18 column (100 × 2.1 mm; i.d., 1.8 μm) with a mobile phase of methanol:0.1% formic acid (55:45, v/v) at a flow rate of 0.3 mL/min. Calibration curves ranging from 5.20 to 2080 ng/mL for β-asarone and from 3.68 to 1470 ng/mL for α-asarone were linear (r2 ≥0.9938) with the lower limits of quantification being 5.20 and 3.68 ng/mL for both isomers. Intravenous administration of β-asarone (2.22 mg/kg) and α-asarone (2.36 mg/kg) in rats yielded half-lives of 13.40±4.11 min and 28.88±7.82 min with clearance values of 0.196± 0.062 mL/min/kg and 0.112±0.012 mL/min/kg for β-asarone and α-asarone, respectively.
      PubDate: 2017-10-12T22:55:32.615842-05:
      DOI: 10.1002/bmc.4115
  • Metabolic -Analysis of the anti-depressive effects of Yangxinshi Tablet in
           a vascular depression model in mice
    • Authors: Hongli Du; Hai Zhang, Yahong Zhao, Min Liu, Anni Chen, Shiyu Liu, Dan Xue, Yanjun Liu, Guoqing Zhang
      Abstract: In recent years, vascular depression has become the focus of international attention. Yangxinshi Tablet (YXST) is usually used in clinic for treatment of arrhythmia and heart failure, but we found that it also has anti-depressive effect in this study. The objective of the study was to identify biomarkers related to vascular depression in hippocampus and explore the anti-depressive effects of YXST on the mice model.Untargeted metabolomics based on UHPLC-Q-TOF/MS was applied to identify significant differential biomarkers between model group and control group. Unsupervised principle component analysis (PCA) was used to scan the tendency of groups and partial least squares-discriminant analysis (PLS-DA) to distinguish the vascular depressive mice and the sham.PCA stores showed clear differences in the metabolism between the vascular depressive mice and sham groups. PLS-DA model exhibited 38 metabolites as the biomarkers to distinguish the vascular depressive mice and the sham. What's more, YXST could significantly regulate 22 metabolites to normal levels.The results suggested that YXST played comprehensive anti-depressive effect on the vascular depression via regulation of multiple metabolic pathways including amino acid, tricarboxylic acid cycle, and phosphoglyceride metabolisms. These findings provided insight into the pathophysiological mechanism underlying vascular depression and mechanism of YXST.
      PubDate: 2017-10-09T16:45:23.608962-05:
      DOI: 10.1002/bmc.4114
  • UPLC-HR-MS/MS-based determination study on the metabolism of four
           synthetic cannabinoids ADB-FUBICA, AB-FUBICA, AB-BICA and ADB-BICA, by
           human liver microsomes
    • Authors: Jing Li; Cuimei Liu, Tao Li, Zhendong Hua
      Abstract: Since 2012, several cannabimimetic indazole and indole derivatives with valine amino acid amide residue have emerged in the illicit drug market, and gradually replaced the old generations of synthetic cannabinoids (SCs) with naphthyl or adamantine groups. Among them, ADB-FUBICA, AB-FUBICA, AB-BICA and ADB-BICA were detected in China recently, but unfortunately no information about their in vitro human metabolism is available for now. Therefore, biomonitoring studies to screen their consumption lack any information about the potential biomarkers (e.g.metabolites) to target. To bridge this gap, we investigated their phase I metabolism by incubating with human liver microsomes, and the metabolites were identified by Ultra Performance liquid chromatography-high resolution-tandem mass spectrometry (UPLC-HR-MS/MS).Metabolites generated by N-dealkylation and hydroxylation on the 1-amino-alkyl moiety were found to be predominant for all these four substances, and others which underwent hydroxylation, amide hydrolysis and dehydrogenation were also observed in our investigation. Based on our research, we recommend that the N-dealkylation and hydroxylation metabolites are suitable and appropriate analytical markers for monitoring their intake.
      PubDate: 2017-10-09T12:10:20.758166-05:
      DOI: 10.1002/bmc.4113
  • Screening of analgesic and anti-inflammatory active component in Fructus
           Alpiniae zerumbet based on spectrum-effect relationship and GC-MS
    • Authors: Rui-yao Xiao; Ling-jing Wu, Xiao-xiao Hong, Ling Tao, Peng Luo, Xiang-chun Shen
      Abstract: Fructus Alpiniae zerumbet was widely used in Guizhou province as miao folk herb with anti-inflammatory, analgesic, protection against cardiovascular diseases, anti-hypertension, and antioxidant activities. To further investigate the chemical material basis, the spectrum-effect relationship was established using grey relational analysis between the chromatographic fingerprint and its bioactivities. Herein, the fingerprints of essential oils from Fructus Alpiniae zerumbet (EOFAZ) from various sources were determined by gas chromatography mass spectrometry (GC-MS), and the analgesic and anti-inflammatory bioactivities were investigated by the mice model of acetic acid-induced writhing test and dimethylbenzene-induced mice ear edema test. Finally, 17 common peaks were identified from 9 batches of Alpiniae zerumbet, by comparing with the standard mass spectra in Nist2005, Wiley275 library. Meanwhile, the results showed significant analgesic and anti-inflammatory effects all of the different resources of EOFAZ. In particularly, Peak 1 (alpha-pipene), peak 3 (beta-pinene), peak 9 (camphor) and peak 16 (alpha-cadinol) might be the main bioactive ingredients for analgesic and anti-inflammatory activities. The model of the spectrum–effect relationships of EOFAZ was successfully discovered, which provided a novel platform for finding the bioactive components, a theoretical foundation for its further study and helping for quality control of Fructus Alpiniae zerumbet.
      PubDate: 2017-10-09T10:30:59.251513-05:
      DOI: 10.1002/bmc.4112
  • A target and non-target strategy for identification or characterization of
           the chemical ingredients in Chinese herb preparation Shuang-Huang-Lian
           oral liquid by ultra-performance liquid chromatography-quadrupole
           time-of-flight mass spectrometry
    • Authors: Feng-xiang Zhang; Min Li, Zhi-hong Yao, Chang Li, Li-rui Qiao, Xiu-yu Shen, Kate Yu, Yi Dai, Xin-sheng Yao
      Abstract: A target and non-target strategy based on in-house chemical components library was developed for rapid and comprehensive analysis of complicated components from traditional Chinese medicine (TCM) preparation Shuang-Huang-Lian oral liquid (SHL). The sample was analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Qtof MS) using generic acquisition parameters. Automated detection and data filtering were performed on the UNIFITM software and the detected peaks were evaluated against an in-house library. As a result, a total of 170 chemical components (110 target compounds and 60 non-target ones) were identified or tentatively characterized, including 54 flavonoids, 30 phenylethanoid glycosides, 16 iridoid glycosides, 14 lignans, 32 organic acids, 19 triterpenoid saponins and 5 other types compounds. Among them, 44 compounds were further confirmed by comparison with reference standards. It demonstrated that this systematical approach could be successfully applied for rapid identification of multiple compounds in TCM and its preparations. Furthermore, this work established the foundation for the further investigation on the metabolic fates of multiple ingredients in SHL.
      PubDate: 2017-10-09T10:10:25.734863-05:
      DOI: 10.1002/bmc.4110
  • A review of bioanalytical quantitative methods for selected sphingosine
           1-phosphate (S1P1) receptor modulators
    • Authors: Ranjeet Prasad Dash; Nuggehally R. Srinivas, Rana Rais
      Abstract: Sphingosine 1-phosphate (S1P1) modulators provide an emerging therapeutic approach for various autoimmune disorders such as multiple sclerosis and psoriasis. Fingolimod is the first approved orally active, selective and potent drug of this class. Other drugs belonging to this class include siponimod, ponesimod, ceralifimod, amiselimod, CS-0777 and GSK2018682. However, due to the high protein binding, polarity and zwitter-ionic nature of the phosphate metabolite of parent drugs, it becomes challenging to optimize the extraction method for this class of compounds. Although, there are individual published bioanalytical methods for the analysis of selected S1P1 modulators to support preclinical and clinical drug development, no extensive review compiling all the bioanalytical methods for the important drugs in the class is available. Thus, we attempted to prepare a comprehensive review on various bioanalytical methods for selected S1P1 modulators which will provide all the relevant bioanalytical information as required by bioanalytical researchers. This review focuses on the various liquid chromatography with tandem mass spectrometry (LC-MS/MS) methods that have been used to quantify S1P1 modulators in various biological matrices. Extraction methods included liquid-liquid extraction, solid-phase extraction and one step protein precipitation for extracting the analytes. This review captures key information regarding sample processing options and chromatographic/detection conditions.
      PubDate: 2017-10-09T02:30:18.4958-05:00
      DOI: 10.1002/bmc.4109
  • Metabolite profiling of ginsenosides in rat plasma, urine, and faeces by
           LC-MS/MS and its application to a pharmacokinetic study after oral
           administration of Panax ginseng extract
    • Authors: Wei-Wei Dong; Xiong-Zhe Han, Jinhua Zhao, Fei-Liang Zhong, Rui Ma, Songquan Wu, Donghao Li, Lin-Hu Quan, Jun Jiang
      Abstract: Panax ginseng has been widely consumed as a functional food in the form of tea, powder, capsules, among others, and possesses a range of pharmacological activities including adaptogenic, immune-modulatory, anti-tumour, anti-aging, and anti-inflammatory effects. The aim of this study was to identify and quantify the major ginsenosides and their metabolites in rat plasma, urine, and faeces after administration of Panax ginseng extract by using LC–MS/MS. We collected rat plasma samples at 0.5, 1, 2, 4, 8, 12, 24, and 48 h, and the amounts of urine and faecal samples accumulated in 24 h. Fourteen major ginsenosides and their metabolites were observed in faecal samples at high levels; however, low levels of eleven ginsenosides were detected in urine samples. The pharmacokinetics of the major ginsenosides and their metabolites was investigated in plasma. The results indicated that Cmax, Tmax, and AUC of compound K were significantly greater than those of other ginsenosides. This study thus provides valuable information for drug development and clinical application of Panax ginseng.
      PubDate: 2017-10-07T09:00:28.015701-05:
      DOI: 10.1002/bmc.4105
  • Quantification and application of a liquid chromatography–tandem mass
           spectrometric method for the determination of WKYMVm peptide in rat using
           solid phase extraction
    • Authors: Byeong Ill Lee; Min-Ho Park, Soon Chul Heo, Yuri Park, Seok Ho Shin, Jin Ju Byeon, Jae Ho Kim, Young G. Shin
      Abstract: A liquid chromatographic-electrospray ionization-time-of-flight/mass spectrometric (LC-ESI-TOF/MS) method was developed and applied for the determination of WKYMVm peptide in rat plasma to support preclinical pharmacokinetics studies. The method consisted of micro-elution solid phase extraction (SPE) for sample preparation and LC-ESI-TOF/MS in the positive ion mode for analysis. Phenanthroline (10mg/mL) was added to rat blood immediately for plasma preparation followed by addition of trace amount of 2M hydrogen chloride (HCl) to plasma before SPE for the stability of WKYMVm peptide. Then, sample preparation using micro-elution SPE was performed with verapamil as an internal standard.A quadratic regression (weighted 1/concentration2), with an equation y=ax2+bx+c, was used to fit calibration curves over the concentration range of 3.02~2200 ng/mL for WKYMVm peptide. The quantification run met the acceptance criteria of ±25 % accuracy and precision values. For quality control samples at 15, 165, and 1820 ng/mL from the quantification experiment, the within-run and the between-run accuracy ranged from 92.5 to 123.4 % with precision values ≤15.1 % for WKYMVm peptide from the nominal values.This novel LC-ESI-TOF/MS method was successfully applied to evaluate the pharmacokinetics of WKYMVm peptide in rat plasma.
      PubDate: 2017-10-04T10:20:21.25618-05:0
      DOI: 10.1002/bmc.4107
  • Simultaneous determination and pharmacokinetic study of three flavonoid
           glycosides in rat plasma by LC-MS/MS after oral administration of Rubus
           chingii Hu extract
    • Authors: Tao Zan; Li Piao, Yuntao Wei, Yue Gu, Baohua Liu, Daqing Jiang
      Abstract: A simple and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of isoquercitrin, kaempferol-3-O-rutinoside, and tiliroside in rat plasma. Plasma samples were deproteinized with methanol and separated on a Hypersil Gold C18 column (2.1 mm × 50 mm, i.d., 3.0 μm) using gradient elution with the mobile phase of water and methanol at a flow rate of 0.4 mL/min. Mass spectrometric detection was performed with negative ion electrospray ionization in selected reaction monitoring mode. All analytes showed good linearity over their investigated concentration ranges (r2>0.99). The lower limit of quantification was 1.0 ng/mL for isoquercitrin, 2.0 ng/mL for kaempferol-3-O-rutinoside and tiliroside, respectively. Intra- and inter-day precisions were less than 8.2% and accuracy ranged from –11.5% to 9.7%. The mean extraction recoveries of analytes and IS from rat plasma were more than 80.4%. The assay was successfully applied to investigate the pharmacokinetic study of the three ingredients after oral administration of Rubus chingii Hu to rats.
      PubDate: 2017-10-04T10:05:28.719656-05:
      DOI: 10.1002/bmc.4106
  • Ketamine and Norketamine Stability in Whole Blood at Ambient and 4°C
    • Authors: Benjamin Duy Tran; Ganesh S. Moorthy, Athena F. Zuppa
      Abstract: A study was implemented to describe the pharmacokinetics (PK) of ketamine (K) and its metabolite norketamine (NK) in critically ill adults. Conducting studies in these subjects is hindered by the immediate need to process and freeze samples obtained in a busy intensive care setting. The ability to store unprocessed samples at room temperature for an extended time period would overcome this barrier. Stability and blood to plasma partitioning of K and NK were investigated in whole blood up to 120 h at room temperature and 4 °C. Whole blood was spiked with K and NK (1,000 ng/mL each). Blood samples were aliquoted at different time points (0 to 120 h), extracted, and analyzed using a validated high performance liquid chromatography tandem mass spectrometry assay. The study demonstrated the stability of both K and NK in whole blood up to 120 hours. These in vitro studies suggest that the concentrations of K and NK measured in the PK samples are reliable. The established stability results were successfully employed to investigate K and NK pharmacology studies in critically ill adults.
      PubDate: 2017-10-04T09:50:41.023925-05:
      DOI: 10.1002/bmc.4104
  • HPLC-MS/MS analysis of peramivir in rat plasma: elimination of matrix
           effect using the phospholipid-removal solid-phase extraction method
    • Authors: Mingdao Lei; Wei Gan, Yongbing Sun
      Abstract: A simple HPLC-MS/MS method has been developed for the determination of peramivir in rat plasma in the present study. The analytes were separated on a C18 column (50×2.1mm, 1.7 μm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source was applied for the detection. A phospholipid-free cartridge SPE was used to pretreat the plasma and eliminate the endogenous phospholipid. The in-source collisionally induced dissociation (CID) approach showed that this pretreatment could result in the negligible ion suppression from the extracted sample, and could bring cleaner samples when compared with the protein precipitation. The method was linear over the concentration ranges of 0.12-1200.0 ng/mL for peramivir. The method was validated and successfully applied to the pharmacokinetic study after peramivir was orally and intravenously administered to the Sprague-Dawley rats, respectively.
      PubDate: 2017-10-04T09:31:18.695135-05:
      DOI: 10.1002/bmc.4103
  • Simultaneous LC-MS/MS analysis of eicosanoids and related metabolites in
           human serum, sputum, and BALF
    • Authors: Rhishikesh Thakare; Yashpal S. Chhonker, Nagsen Gautam, Amy Nelson, Richard Casaburi, Gerard Criner, Mark T. Dransfield, Barry Make, Kendra K. Schmid, Stephen I. Rennard, Yazen Alnouti
      Abstract: The differences among individual eicosanoids in eliciting different physiological and pathological responses are largely unknown because of the lack of valid and simple analytical methods for the quantification of individual eicosanoids and their metabolites in serum, sputum, and BALF. Therefore, a simple and sensitive LC–MS/MS method for the simultaneous quantification of 34 eicosanoids in human serum, sputum, and BALF was developed and validated. This method is valid and sensitive with a limit of quantification ranging from 0.2 to 3 ng/ml for the various analytes, has a large dynamic range (500 ng/ml), and a short run time (25 min). The intra-day and inter-day accuracy and precision values met the acceptance criteria according to US Food and Drug Administration guidelines. Using this method, detailed eicosanoid profiles were quantified in serum, sputum, and BALF from a pilot human study. In summary, a reliable and simple LC–MS/MS method to quantify major eicosanoids and their metabolites was developed and applied to quantify eicosanoids in human various fluids demonstrating suitability to assess eicosanoid biomarkers in human clinical trials.
      PubDate: 2017-10-04T03:12:21.02322-05:0
      DOI: 10.1002/bmc.4102
  • Chromatographic determination, decline dynamic, and risk assessment of
           sulfoxaflor in Asian pear and oriental melon
    • Authors: Md. Humayun Kabir; A.M. Abd El-Aty, Md. Musfiqur Rahman, Hyung Suk Chung, Han Sol Lee, Sung Woo Kim, Hee-Ra Chang, Ho-Chul Shin, Sung Shik Shin, Jae-Han Shim
      Abstract: The dissipation pattern of sulfoxaflor in Asian pear cultivated in an open field conditions and in oriental melon grown under plastic house conditions was each studied in two different locations. Residues in field-treated samples were determined using liquid chromatography (LC) coupled with an ultraviolet detector (UVD) and confirmed by liquid chromatography–tandem mass spectrometry (LC-MS/MS). A calibration curve for sulfoxaflor was linear over the concentration range 0.1–5.0 mg/L, with a coefficient of determination (R2 ≥) of 0.9999. The limits of detection (LOD) and quantification (LOQ) were 0.007 and 0.02 mg/kg, respectively. Recoveries at three fortification levels [LOQ, 10× LOQ, and maximum residue limit (MRL)] ranged from 70.5% to 86.2%, with a relative standard deviation (RSD) ≤5.8%. The dissipation half-lives were 10.8 and 7.9 days in pear and 5.4 and 5.9 days in oriental melon, at sites 1 and 2, respectively. Based on a pre-harvest residue limit (PHRL) curve, it was predicted that if the residues at 10 days before harvest in Asian pear are ˂0.54/0.61 mg/kg and those in oriental melon are ˂1.43/1.26 mg/kg, then the residue level would be below the MRL at harvest. Risk assessment at zero days showed a percentage accepted daily intake of 10.80% in Asian pear and 1.77% and 1.55% in oriental melon, for sites 1 and 2, respectively. These values indicate that the fruits are safe for consumption.
      PubDate: 2017-10-04T02:10:47.124585-05:
      DOI: 10.1002/bmc.4101
  • A Rapid and Simple HPTLC Assay for Therapeutic Drug Monitoring of
           Capecitabine in Colorectal Cancer Patients
    • Authors: Sonali G. Thorat; Rupesh V. Chikhale, Madhukar R. Tajne
      Abstract: Capecitabine is a prodrug of 5-flurouracil, employed as a broad spectrum chemotherapeutic agents. It is also used as monotherapy or a combination chemotherapy agent for treatment of colorectal cancer. Capecitabine is administered in combination with oxaliplatin and hence it becomes essential to determine that co-administration does not affect its metabolism. To determine the plasma concentration of capecitabine a simple HPTLC method was developed and validated. Blood samples from 12 patients with colorectal cancer were collected and analysed by the HPTLC method with a reference internal standard. Out of these 12 patients, 6 were treated with capecitabine monotherapy and another 6 were treated with capecitabine + oxaliplatin combination therapy. The results of analysis indicated that there is no significant drug-drug interaction and the co-administration of oxaliplatin did not affect the metabolism of capecitabine. This method is sensitive, robust and specific and allows analysis of multiple samples simultaneously making it suitable for therapeutic drug monitoring of capecitabine.
      PubDate: 2017-09-22T22:25:20.910084-05:
      DOI: 10.1002/bmc.4100
  • Simultaneous determination of serum propafenone and its metabolites using
           high-performance liquid chromatography
    • Authors: Yuki Shirayama; Kosuke Doki, Yukio Sekiguchi, Kazutaka Aonuma, Yukinao Kohda, Masato Homma
      Abstract: Propafenone, a class Ic antiarrhythmic agent, is metabolized to 5-hydroxypropafeone (5-OHP) and N-depropylpropafenone (NDPP). Simultaneous determination of serum propafenone and its metabolites was performed using high-performance liquid chromatography (HPLC) equipped with a conventional octadecylsilyl silica column and ultraviolet detector. The wavelength was set at 250 nm. Propafenone and its metabolites in the serum were extracted using diethyl ether. The mobile phase solution, comprising 1-pentanesulfonic acid sodium salt (0.1 M), acetonitrile, and acetic acid (280:185:2.5, v/v/v), was pumped at a flow rate of 1 ml/min. The recoveries of propafenone, 5-OHP, and NDPP were greater than 85, 82, and 60%, respectively, with the coefficients of variation (CVs) less than 5.4, 1.9, and 2.9%, respectively. The calibration curves were linear for a concentration range of 12.5–1500 ng/ml for propafenone and 2–500 ng/ml for 5-OHP and NDPP (r> 0.999). CVs in the intra-day assays were 1.0%–3.8% for propafenone, 0.6%–2.0% for 5-OHP, and 0.6%–1.7% for NDPP. CVs in inter-day assays were 1.3%–7.7% for propafenone, 1.1%–6.5% for 5-OHP, and 5.4%–8.0% for NDPP. The present HPLC method can be used to assess the disposition of propafenone and its metabolites for pharmacokinetic studies and therapeutic drug monitoring of propafenone.
      PubDate: 2017-09-19T19:40:30.883166-05:
      DOI: 10.1002/bmc.4099
  • Simple determination of betaine, L-carnitine and choline in human urine
           using self-packed column and column-switching ion chromatography with
           non-suppressed conductivity detection
    • Authors: Dan Wei; Yan Zhu, Ming Guo
      Abstract: A sequential on-line extraction, clean-up and separation system for the determination of betaine, L-carnitine and choline in human urine using column-switching ion chromatography with non-suppressed conductivity detection was developed in this work. Self-packed pretreatment column (50 mm×4.6 mm, i.d.) was used for the extraction and clean-up of betaine, L-carnitine and choline. The separation was achieved using self-packed cationic exchange column (150 mm×4.6 mm, i.d.), followed by non-suppressed conductivity detection. Under optimized experimental conditions, the developed method presented good analytical performance, with excellent linearity in ranged of 0.60-100 μg mL-1 for betaine, 0.75-100 μg mL-1 for L-carnitine and 0.50-100 μg mL-1 for choline, with all correlation coefficient (R2) above 0.99 in urine. The limits of detection (LOD) were of 0.15 μg mL-1 for betaine and 0.20 μg mL-1 for L-carnitine and 0.09 μg mL-1 for choline. The intra- and inter-day accuracy and precision for all quality controls were within ±10.32% and ±9.05%, respectively. Satisfactory recovery was observed between 92.8% and 102.0%. The validated method was successfully applied to the detection of urinary samples from 10 healthy people. The values detected in human urine using the proposed method had a good agreement with the measurement reported previously.
      PubDate: 2017-09-15T20:00:50.715356-05:
      DOI: 10.1002/bmc.4098
  • Dynamic residual pattern of azoxystrobin in Swiss chard with contribution
           to safety evaluation
    • Authors: Waziha Farha; A.M. Abd El-Aty, Md. Musfiqur Rahman, Md. Humayun Kabir, Hyung Suk Chung, Han Sol Lee, Jong-Sup Jeon, Jing Wang, Byung-Joon Chang, Ho-Chul Shin, Jae-Han Shim
      Abstract: This study aimed at quantifying the residual amount of azoxystrobin in Swiss chard samples grown under greenhouse conditions at 2 different locations (Gwangju and Naju, Republic of Korea). Samples were extracted with acetonitrile, separated by salting out, and subjected to purification by using solid-phase extraction (SPE). The analyte was identified using liquid chromatography (LC)-ultraviolet detector (UVD). The linearity of the calibration range was excellent with coefficient of determination (R2) =1.00. Recovery at 3 different spiking levels (0.1, 0.5, and 4 mg/kg) ranged between 82.89 and 109.46% with relative standard deviation (RSD) < 3. The limit of quantification (LOQ), 0.01 mg/kg was considerably much lower than the maximum residue limit (MRL = 50 mg/kg) set by the Korean Ministry of Food and Drug Safety. The developed methodology has been successfully used for field treated leaves, which were collected randomly at 0 to 14 days following azoxystrobin application. The rate of disappearance in/on Swiss chard was ascribed to 1st order kinetics with a half-life of 8 and 5 days, in leaves grown at Gwangju and Naju greenhouses, respectively. Risk assessments revealed that the acceptable daily intake percentage (ADI%) is substantially below the risk level of consumption, at day 0 (in both areas), thus encouraging its safe consumption.
      PubDate: 2017-09-15T19:15:59.880259-05:
      DOI: 10.1002/bmc.4092
  • Material Basis Studies of Anti-Influenza A Active Ingredients in Tanreqing
    • Authors: Haiyan Zhu; Mingchang Chen, Xunlong Shi, Chenchen Shi, Chenggang Huang
      Abstract: Tanreqing Injection (TRQ) has been used primarily in treating infections of the upper respiratory tract and serious influenza in China, as a classical compound herbal recipe. TRQ had been demonstrated its effects of clearing heat, eliminating phlegm, detoxification, reducing inflammation and alleviating cough. The survival rate, histopathology of lungs and viral titers in mice were evaluated in this study to verify the curative effect of TRQ. However, there is not enough information about the components. In the present study, a high-performance and practical LC/QTOF/MS method was developed for characterization and identification of the natural ingredients in TRQ. A total of 60 compounds, including 10 amino acids, 10 iridoid glucosides, 14 flavonoids, 13 other phenolic compounds, 10 steroid acids and 3 other compounds were characterized and identified. And we confirmed the material basis of Anti-influenza A active ingredients in TRQ. Therefore, we have developed an accurate analytical method. LC/QTOF/MS could be applied for identification the complex components in Traditional Chinese Medicine.
      PubDate: 2017-09-15T15:02:23.487024-05:
      DOI: 10.1002/bmc.4097
  • Quantification through TLC-Densitometric analysis, repellency and
           anticholinesterase activity of the homemade extract of Indian cloves
    • Authors: Raphael S. Affonso; Josélia A. Lima, Bruno Lessa, João V.O. Caetano, Marcos T. Obara, Andrea Nóbrega, Eugenie Nepominova, Kamil Musilek, Kamil Kuca, Gláucia Barbosa Candido Alves Slana, Tanos C.C. França
      Abstract: The rise of mosquito's transmitted diseases, like dengue, zika and chikungunya in Brazil in the last years has increased the concerns on protection against mosquito's bites. However, the prohibitive prices of the commercially available repellents for the majority of the Brazilian population, has provoked a search for cheaper solutions, like the use of the homemade ethanolic extract of Indian clove (Syzygium aromaticum L.) as repellent, which has been reported as quite efficient by the local press. In order to verify this, we performed here, the quantification of the main components of this extract through high-performance thin-layer chromatography (HPTLC)-densitometry and evaluated its efficiency as repellent, as well as the acetylcholinesterase (AChE) inhibition capacity. Our results have proved HPTLC-densitometry as an efficient and appropriate method for this quantification and confirmed the repellency activity as well as its capacity of AChE inhibition.
      PubDate: 2017-09-15T01:15:25.985587-05:
      DOI: 10.1002/bmc.4096
  • Overcoming interference of plasma phospholipids using HybridSPE for the
           determination of trimetazidine by UPLC-MS/MS
    • Authors: Pravin G. Vanol; Manish Yadav, Mallika Sanyal, Priyanka A. Shah, Pranav S. Shrivastav
      Abstract: An improved, precise and reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the quantification of trimetazidine, using trimetazidine-d8 as the internal standard (IS). Interference due to plasma phospholipids during sample preparation was overcome by using hybrid solid phase extraction-phospholipid ultra cartridge. The mean extraction recovery of trimetazidine (98.66 %) and trimetazidine-d8 (97.63 %) from spiked plasma was consistent and reproducible. Chromatographic analysis was performed on UPLC Ethylene Bridged Hybrid (BEH) C18 (50 × 2.1 mm, 1.7 μm) column with isocratic elution using acetonitrile-5 mM ammonium formate, pH 3.5 (40:60, v/v) as the mobile phase. The parent product ion transitions for trimetazidine (m/z 267.1181.1) and trimetazidine-d8 (m/z 275.2181.1) were monitored on a triple quadrupole mass spectrometer with electrospray ionization functioning in the positive multiple reaction monitoring mode. The linearity of the method was established in the concentration range of 0.05-100 ng/mL for trimetazidine. The intra-batch and inter-batch accuracy and precision (% CV) ranged from 97.3-103.1 % and 1.7-5.3 %, respectively. Qualitative and quantitative assessment of matrix effect showed no interference of endogenous/exogenous components. The developed method was used to measure plasma trimetazidine concentration for a bioequivalence study with 12 healthy subjects.
      PubDate: 2017-09-14T06:45:48.483959-05:
      DOI: 10.1002/bmc.4095
  • Anti-inflammatory activities and glycerophospholipids metabolism in
           KLA-stimulated RAW 264.7 macrophage cells by diarylheptanoids from the
           rhizomes of Alpinia officinarum
    • Authors: Guogai Zhang; Lifang Zhao, Jiancheng Zhu, Yifan Feng, Xia Wu
      Abstract: Alpinia officinarum was used for anti-inflammatory activity historically in China. Diarylheptanoids isolated from Alpinia officinarum play important biological roles in prevention and treatment of inflammatory disorders. Seven diarylheptanoids (1-7) were isolated from Alpinia officinarum. The cell viabilities and anti-inflammatory activities of diarylheptanoids were evaluated by MTT assay and tumor necrosis factor-a (TNF-a) production in KLA-stimulated RAW 264.7 cells in vitro. Meanwhile, the relationships between their anti-inflammatories and structure-activities were discussed. The result indicated that compounds 1 and 3-7 had significant anti-inflammatory activities. The relationships between inflammation and phospholipids metabolism were elucidated by multivariate data analysis. 22 potential biomarkers were identified in inflammatory group vs. blank group, and 11 potential biomarkers were identified for inflammatory group vs. drug-treatment groups. 10 common phospholipids were characterized. On the basis of previous study in our laboratory, we found that phosphatidylethanolamine (PE, 18:0/18:1) might be the important glycerophospholipid biomarker in inflammation. In this study, we firstly combined anti-inflammatory activities and glycerophospholipids changes of traditional Chinese medicine. And this work suggested that anti-inflammatory activities of diarylheptanoids might be significantly related to glycerophospholipids and could provide a useful data base for investigating anti-inflammatory effects of traditional Chinese medicine.
      PubDate: 2017-09-14T06:10:49.926975-05:
      DOI: 10.1002/bmc.4094
  • Intergrated metabonomic study of the effects of Guizhi Fuling capsule
           intervention on primary dysmenorrheal using RP-UPLC-MS complementary with
           HILIC-UPLC-MS technique
    • Authors: Lang Lang; Zhaorui Meng, Lan Sun, Wei Xiao, Longshan Zhao, Zhili Xiong
      Abstract: Guizhi Fuling capsule (GFC), developed from the traditional Chinese prescription of Guizhi Fuling Wan, has been commonly used for the treatment of primary dysmenorrheal (PD). However, the intervention effective mechanism in vivo has not been well elucidated. In this study, an integrated plasma metabonomic strategy based on RP-UPLC-MS coupled with HILIC-UPLC-MS technique has been developed to investigate the global therapeutic effects and intervention mechanisms of Guizhi Fuling capsule (GFC) on dysmenorrhea rats induced by oxytocin. The total twenty potential biomarkers were identified and primarily related to sphingolipid metabolism, steroid hormone biosynthesis, glycerophospholipid metabolism, amino acid metabolism, lipid metabolism and energy metabolism. The results showed that the GFC has therapeutic effects on rat with dysmenorrhea via the regulation of multiple metabolic pathways. Some new potential biomarkers associated with primary dysmenorrhea such as phenylalanine, tryptophan, taurine, carnitine, betaine, creatine and creatinine have been discovered in this study for the first time. This study provides a metabonomic platform based on RP-UPLC-MS complementary with HILIC-UPLC-MS technique to investigate both nonpolar and polar compounds, so as to get a more comprehensive metabolite information for yielding insight into the pathophysiology of PD and assessing the efficacy of GFC on PD rats.
      PubDate: 2017-09-14T04:55:23.511451-05:
      DOI: 10.1002/bmc.4093
  • Simultaneous determination of boscalid and fludioxonil in grape and soil
           under field conditions by gas chromatography/tandem triple quadrupole mass
    • Authors: Haizhen Zhang; A'wei Zhang, Min Huang, Weiwei Yu, Zhurui Li, Sizhuo Wu, Kunming Zhang, Kankan Zhang, Deyu Hu
      Abstract: A gas chromatography–tandem mass spectrometry method was developed and validated to simultaneously determine boscalid and fludioxonil in grape and soil samples. These samples were extracted with 10 mL of acetonitrile and purified using a mixed primary secondary amine/octadecylsilane sorbent. The method showed good linearity (R2>0.99) in the calibration range 0.005–2 μg/mL for both pesticides. The limits of detection and quantification for the two analytes in grape and soil were 0.006 mg/kg and 0.02 mg/kg, respectively. Fungicide recoveries in grape and soil were 81.18–92.11% for boscalid and 82.73–97.67% for fludioxonil with relative standard deviations of 1.31–10.31%. The established method was successfully applied to the residual analysis of boscalid and fludioxonil in real grape and soil samples. The terminal residue concentrations of boscalid and fludioxonil in grape samples collected from Anhui and Guizhou were below 5 mg/kg (the maximum residue limit (MRL) set by China) seven days after the last application and 1 mg/kg (MRL set by USA) 14 days after the last application, respectively. These results could provide guidance for the proper and safe use of boscalid and fludioxonil in grape and help the Chinese government to establish an MRL for fludioxonil in grape.
      PubDate: 2017-09-14T03:56:59.519212-05:
      DOI: 10.1002/bmc.4091
  • Bioassay, determination and separation of enantiomers of atenolol by
           direct and indirect approaches using liquid chromatography: A review
    • Authors: Sonika Batra; Ravi Bhushan
      Abstract: Atenolol, a β-adrenergic receptor antagonist, is a chiral compound used for the treatment of cardiovascular diseases and to treat hypertension, coronary heart disease, arrhythmias, sinus tachycardia and myocardial infarction, where it acts preferentially upon the β-adrenergic receptors in the heart. It is marketed as a racemate, but only (S)-enantiomer of (RS)-atenolol is responsible for the β-adrenoceptor blocking activity. Different chromatographic methods have been applied for separation and determination of enantiomers. In this article a review is presented on liquid chromatographic methods for enantioseparation of (RS)-atenolol by both direct and indirect approaches involving practical applications of several chiral stationary phases (CSPs), chiral derivatization reagents, and ligand exchange and impregnation methods. These include methods using both HPLC and TLC for separation, determination and bioassay of enantiomers of atenolol. Besides, some aspects of enantioseparation under achiral phases of liquid chromatography has been briefly mentioned as applicable to (RS)-atenolol. This review provides current available enantioseparation choices not only for (RS)-atenolol but for other applicable racemic drugs.
      PubDate: 2017-09-14T03:07:45.906884-05:
      DOI: 10.1002/bmc.4090
  • Simultaneous determination of glaucocalyxin A and glaucocalyxin B in rat
           plasma by LC-MS/MS and its application to a pharmacokinetic study after
           oral administration of Rabdosia japonica extract
    • Authors: Weili Huang; Xiaohui Guan, Yongchen Lv
      Abstract: A specific and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the analysis of glaucocalyxin A and glaucocalyxin B in rat plasma using praeruptorin A as an internal standard. Separation was performed on a Hypurity C18 column (2.1 mm × 50 mm, 5 μm) with isocratic elution using 0.2% formic acid in water-acetonitrile (20:80, v/v). Mass spectrometric detection was conducted using selected reaction monitoring via an electrospray ionization source. Both analytes exhibited good linearity within their concentration ranges (r2> 0.9932). The lower limit of quantitation (LLOQ) of glaucocalyxin A and glaucocalyxin B was1.10 ng/mL. Intra- and inter-day precision exhibited an RSD within 14.5%, and the accuracy (RE) ranged from –12.1% to 15.0% at the LLOQ and three QC levels. The developed assay was successfully applied to a pharmacokinetic study of glaucocalyxin A and glaucocalyxin B in rats after oral administration of Rabdosia japonica extract.
      PubDate: 2017-09-05T17:00:24.483978-05:
      DOI: 10.1002/bmc.4089
  • Chromatographic approaches for the characterization and quality control of
           therapeutic oligonucleotide impurities
    • Authors: N.M. El Zahar; N. Magdy, A.M. El-Kosasy, Michael G. Bartlett
      Abstract: Phosphorothioate (PS) oligonucleotides are a rapidly rising class of drugs with significant therapeutic applications. However, due to their complex structure and multi-step synthesis and purification processes, generation of low level impurities and degradation products are common. Therefore, they require significant investment in quality control and impurity identification. This requires the development of advanced methods for analysis, characterization and quantitation. In addition, the presence of the PS linkage leads to the formation of chiral centers which can affect their biological properties and therapeutic efficiency.In this review, the different types of oligonucleotide impurities and degradation products, with an emphasis on their origin, mechanism of formation and methods to reduce, prevent or even eliminate their production, will be extensively discussed. This review will focus mainly on the application of chromatographic techniques to determine these impurities but will also discuss other approaches such as mass spectrometry, capillary electrophoresis and nuclear magnetic resonance spectroscopy. Finally, the chirality and formation of diastereomer mixtures of PS oligonucleotides will be covered as well as approaches used for their characterization and the application for the development of stereochemically-controlled PS oligonucleotides.
      PubDate: 2017-09-04T06:01:06.901561-05:
      DOI: 10.1002/bmc.4088
  • Exploring the mechanism of Jieduquyuziyin Prescription on Systemic Lupus
           Erythematosus by GC-MS-based Urine Metabolomics
    • Authors: Jing Wei; Jun Gao, Xinghong Ding
      Abstract: A urine metabolomics method based on gas chromatography mass spectrometry (GC-MS) was developed in order to investigate the metabolites characters of systemic lupus erythematosus (SLE) and therapeutic effects of jieduquyuziyin prescription (JP). The urinary metabolic profiles in urine specimens of the SLE model mice (MRL/lpr) group, prednisone acetate (PA)-treated SLE mice group, JP-treated SLE mice group, and control group (C57BL/6 J) after the administration were analyzed by GC-MS. These metabolic profiles were then processed by multivariate analysis, in particular Mass Profiler Professional (MPP), SIMCA-P and partial least-squares discriminant analysis (PLS-DA). According to the PLS-DA results, the SLE model group and the control group were obviously separated, indicating that the incidence of SLE had a greater impact on the metabolic network, and the SLE model group had significant difference compared with the control group in urine metabolites. 11 differential metabolites were identified to be related to SLE. And the results of differential metabolite identification showed that the metabolites were mainly related to energy metabolism and amino acid metabolism pathway. These results can provide an experimental basis for further exploring the mechanism of traditional Chinese medicine (TCM) in the treatment of SLE.
      PubDate: 2017-09-04T05:40:59.891712-05:
      DOI: 10.1002/bmc.4087
  • Ultra performance liquid chromatography-tandem mass spectrometry assay for
           determination of plasma nomegestrol acetate and estradiol in healthy
           postmenopausal women
    • Authors: Sneha G. Nair; Daxesh P. Patel, Mallika Sanyal, Puran Singhal, Pranav S. Shrivastav
      Abstract: A highly sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry method is described for the simultaneous determination of nomegestrol acetate (NOMAC), a highly selective progestogen, and estradiol (E2), a natural estrogen in human plasma. NOMAC was obtained from plasma by solid phase extraction, while E2 was first separated by liquid-liquid extraction with methyl tert-butyl ether followed by derivatization with dansyl chloride. Deuterated internal standards, NOMAC-d5 and E2-d4 were used for better control of extraction conditions and ionization efficiency. The assay recovery of the analytes was within 90-99 %. The analytes were separated on UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column using a mobile phase comprising of acetonitrile and 3.0 mM ammonium trifluoroacetate in water (80:20, v/v) with a resolution factor (Rs) of 3.21. The calibration curves were linear from 0.01-10.0 ng/mL for NOMAC and 1.00-1000 pg/mL for E2, respectively. The intra-batch and inter-batch precision was ≤5.8 % and the accuracy of quality control samples ranged from 96.7 to 103.4 % for both the analytes. The practical applicability of the method is demonstrated by analyzing samples from 18 healthy postmenopausal women after oral administration of 2.5 mg nomegestrol acetate and 1.5 mg estradiol film coated tablets under fasting.
      PubDate: 2017-09-04T05:26:05.299405-05:
      DOI: 10.1002/bmc.4086
  • Metabonomic analysis of serum reveals antifatigue effects of Yi Guan Jian
           on fatigue mice using Gas Chromatography coupled to Mass spectrometry
    • Authors: Sufang Shui; Xiaorong Cai, Rongqing Huang, Bingkun Xiao, Jianyun Yang
      Abstract: Yi Guan Jian (YGJ), one of the most commonly used traditional Chinese medicines (TCM), has been reported to possess significant antifatigue effects in the eastern. However, the mechanisms underlying its antifatigue effects remain largely unresolved. In this study, a metabonomics approach, involving gas chromatography coupled to mass spectrometry (GC/MS) and a multivariate statistical technique, was developed to estimate the extent to which YGJ alleviated the exhausting swimming induced fatigue of mice. High dose treatment with YGJ significantly extended the swimming time of fatigued mice. Significant alterations of metabolites involving amino acids, organic acids and carbohydrates were observed in the serum of fatigued mice, which was reversed by YGJ treatment while biochemical indexes returned to normal. These metabolic changes suggest that the antifatigue effect of YGJ is associated with the impairement of amino acid, organic acids and carbohydrates. It also appears that YGJ can induce significant metabolic alterations independent of the exhausting swimming induced metabolic changes. The significantly altered metabolites induced by YGJ intervention include L-2-Amino-acetoacetate, taurine, fumaric acid, malic acid, oxoadipic acid, L-Aspartate, all of which are associated with antifatigue properties. This suggests that YGJ exerts chemopreventive effects via antifatigue mechanisms.
      PubDate: 2017-09-03T19:45:20.469491-05:
      DOI: 10.1002/bmc.4085
  • Development and validation of a simple high-performance liquid
           chromatography analytical method for simultaneous determination of
           phytosterols, cholesterol, and squalene in parenteral lipid emulsions
    • Authors: Ana Novak; Mercè Gutiérrez-Zamora, Lluís Domenech, Josep M. Suñé-Negre, Montserrat Miñarro, Encarna García-Montoya, Josep M. Llop, Josep R. Ticó, Pilar Pérez-Lozano
      Abstract: A simple analytical method for simultaneous determination of phytosterols, cholesterol, and squalene in lipid emulsions was developed due to increased interest in their clinical effects. Method development was based on commonly used stationary (C18, C8 and phenyl) and mobile phases (mixtures of acetonitrile, methanol, and water) under isocratic conditions. Differences in stationary phases resulted in peak overlapping or coelution of different peaks. The best separation of all analyzed compounds was achieved on Zorbax Eclipse XDB C8 (150 x 4.6 mm, 5 μm; Agilent) and ACN/H2O/MeOH = 80:19.5:0.5 (v/v/v). In order to achieve a shorter time of analysis, the method was further optimized and gradient separation was established. The optimized analytical method was validated and tested for routine use in lipid emulsion analyses.
      PubDate: 2017-08-30T08:40:45.82651-05:0
      DOI: 10.1002/bmc.4084
  • Simultaneous determination of baicalin, baicalein, wogonoside, wogonin,
           scutellarin, berberine, coptisine, ginsenoside Rb1 and ginsenoside Re of
           Banxia xiexin decoction in rat plasma by LC-MS/MS and its application to a
           pharmacokinetic study
    • Authors: Ying Wang; Yifan Zhang, Juan Xiao, Ranchi Xu, Qiangli Wang, Xinhong Wang
      Abstract: A rapid and high sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for simultaneous determination of nine active constituents, baicalin, baicalein, wogonoside, wogonin, scutellarin, berberine, coptisine, ginsenoside Rb1 and ginsenoside Re in rat plasma after oral administration of Banxia xiexin decoction(BXD). Biological samples were processed wtih acetone-ethyl acetate (4:1, v/v). The mobile phase consisted of methanol and water (containing 0.1% formic acid) with gradient elution at a flow rate of 0.3 mL/min. Detection was performed on a triple quadrupole mass spectrometer using positive ion and negative ESI in the multiple reaction monitoring(MRM) mode. The calibration curves for all analytes had good linearity (r> 0.9933). The mean recovery of all the nine active ingredients was more than 75.2 %, and the intra- and inter-day precisions (RSD) were within 12.0%, the accuracy was between 87.4% and 110.4%. This method was successfully applied to the pharmacokinetic study after administration of BXD. The results of pharmacokinetic study might be helpful for BXD clinical reasonable application and further studies on mechanism.
      PubDate: 2017-08-28T21:40:51.345738-05:
      DOI: 10.1002/bmc.4083
  • Investigation on pharmacokinetics, tissue distribution and excretion of
           Schisandrin B in rats by HPLC-MS/MS
    • Authors: Zhuo Wang; Linjun You, Yan Chen, Kaiyong Hu, Zhanbo Wang, Yanan Cheng, Jin Yang, Yong Yang, Guangji Wang
      Abstract: Schisandrin B has received great attention owing to its various biological activities recently. The present study was aimed at the formulation development of schisandrin B and investigating the pharmacokinetic profiles, distribution and excretion of schisandrin B in Sprague-Dawley rats. In this study, micronized schisandrin B particles with particle size of 10~20μm were chosen as the research object. Chromatographic separation was carried out on a BDS HYPERSIL C18 column (50×2.1 mm, I.D. 3.5 μm). Schisandrin B and deoxyschizandrin (internal standard, IS) were detected without interference in the multiple reaction monitoring (MRM) mode with positive electrospray ionization. The pharmacokinetic parameters were calculated by a non-compartmental method. The area under concentration-time curve (AUC0-t) and the maximum concentration (Cmax) showed a significant difference in gender. The calculated absolute oral bioavailability of schisandrin B was approximately 55.0% for female rat and 19.3% for male rat. Schisandrin B exhibited linear pharmacokinetics properties within the range of the tested oral dose (10 mg/kg, 20 mg/kg, 40 mg/kg). After oral administration of schisandrin B, it was extensively distributed in ovary and adipose tissue. The result also showed very low urinary, biliary and fecal excretion of schisandrin B implying that schisandrin B was excreted mainly in the forms of metabolites.
      PubDate: 2017-08-22T01:21:07.467598-05:
      DOI: 10.1002/bmc.4069
  • Employment of modified Fe₃O₄ nanoparticles using thermo-sensitive
           polymer for extraction and pre-concentration of cefexime in biological
    • Authors: Saman Naghibi; Hamed Sahebi
      Abstract: Cefexime as a useful antibiotic can be prescribed to treat infections resulted by bacteria. Nowadays nanoparticles have been widely marked as a universal utopia among many scientists. Variety of researches has been taken place to modify nanoparticles to make them functional as extraction and pre-concentration agents and drug carriers. Temperature-sensitive polymer belongs to a group of substances which perform a gigantic change in their physical features in response to the temperature. Recent polymer can be widely used in different areas, including modification of nanoparticles. In order to modify this nanoparticle, grafting copolymerisation of Fe₃O₄ nanoparticles was done using poly (N-Vinylcaprolactam) and 3-allyloxy-1,2-propanediol. Optimum condition for pre-concentration of cefexime was studied. At this optimum condition, extraction recovery of biological samples in range of 71-89% was obtained. Limit of detection and precision of proposed method was 4.5×10-4 μg.mL-1and less than 4.11% (Relative Standard Deviation) respectively. Based on the results from analysis of cefexime, in biological samples, using proposed method, ability of recent method in extraction and pre-concentration of cefexime was confirmed. Also, satisfaction results from in vitro study of drug release in simulated intestine media was obtained
      PubDate: 2017-08-19T10:45:24.475749-05:
      DOI: 10.1002/bmc.4082
  • Quantitative analysis of clofazimine (Lamprene®), an antileprosy agent,
           in human dried blood spots using liquid chromatography-tandem mass
    • Authors: Wenkui Li; John Doherty, Yunlin Fu, Jimmy Flarakos
      Abstract: An LC-MS/MS method was developed and validated for bioanalysis of clofazimine in human DBS samples in support of a clinical study on multidrug-resistant tuberculosis in developing countries. The validated assay dynamic range was from 10.0 to 2000 ng/mL using a 1/8″ DBS punch. The accuracy and precision of the assay were ±11.0 % (bias) and ≤13.5% (CV) for the LLOQs (10.0 ng/mL) and ± 15% (bias) and ≤ 15% (CV) for all other QC levels. The assay was proved to be free from the possible impact due to spot size and storage temperature (e.g., at 60°C, ≤-60°C). The validated assay is well suited for the intended clinical studies where conventional PK sample collection is not feasible.
      PubDate: 2017-08-19T00:50:18.707133-05:
      DOI: 10.1002/bmc.4068
  • Simultaneous determination of morphine-6-D-glucuronide,
           morphine-3-D-glucuronide and morphine in human plasma and urine by
           ultra-performance liquid chromatography-tandem mass spectrometry:
           application to M6G injection pharmacokinetic study.
    • Authors: Wen Xu; Quankun Zhuang, Xia Chen, Ji Jiang, Pei Hu, Hongyun Wang
      Abstract: A robust ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of morphine-6-D-glucuronide (M6G), morphine-3-D-glucuronide (M3G) and morphine (MOR) in human plasma and urine has been developed and validated. The analytes of interest were extracted from plasma by protein precipitation. Urine sample was prepared by dilution. Both plasma and urine samples were chromatographed on an Acquity UPLC HSS T3 column using gradient elution. Detection was performed on a Xevo TQ-S tandem mass spectrometer in multiple reactions monitoring (MRM) mode using positive electrospray ionization (ESI). Matrix interferences were not observed at the retention time of the analytes and internal standard (IS) nalooxone-D5. The lower limit of quantitation (LLOQ) of plasma and urine were 2/0.5/0.5 and 20/4/2 ng/mL for M6G/M3G/MOR, respectively. Calibration curves were linear over the concentration range of 2-2000/0.5-500/0.5-500 and 20-20000/4-4000/2-2000 ng/mL for M6G/M3G/MOR in plasma and urine samples, respectively. The precision was less than 7.14 % and the accuracy was within 85%-115%. Furthermore, stability of the analytes at various conditions, dilution integrity, extraction recovery and matrix effect were assessed. Finally, this quantitative method was successfully applied to the pharmacokinetic study of M6G injection in Chinese non-cancer pain patients.
      PubDate: 2017-08-19T00:20:20.271332-05:
      DOI: 10.1002/bmc.4066
  • Application of HPLC-LTQ Orbitrap MS for metabolic profiles of Polygonum
           multiflora extract in rats
    • Authors: Jing Zhang; Tenghua Wang, Zhiyao Ren, Lu Gong, Juan Huang, Junqi Bai, Xiaohui Qiu, Wen Xu
      Abstract: The root of Polygonum multiflora (PM) is an important Chinese herbal medicine for treatment of various diseases. Extensive pharmacological studies have been conducted and demonstrated that it shows a wide range of bioactivities. Meanwhile, considerable amount of hepatotoxicity cases due to oral administration of PM has been reported and attracted great attention. However, The limited knowledge regarding the metabolism of PM restricts the deeper studies on pharmacological/toxic mechanism and therapeutic material basis. The present study was aimed to develop a high-performance liquid chromatography coupled with linear ion trap -Orbitrap hybrid mass spectrometry method for separation and identification of metabolites in rats urine and plasma after oral administration of PM. Based on the proposed strategy, metabolism profiles of PM in rats were proposed for the first time and 43 metabolites were characterized or tentatively identified. The Phase II metabolism such as glucuronidation, and sulfation are the principal pathways of main components. These findings will be beneficial to further understanding of the pharmacological mechanism and pharmacodynamic material basis of Polygonum multiflorum.
      PubDate: 2017-08-17T20:25:33.834292-05:
      DOI: 10.1002/bmc.4067
  • LC-ESI-MS/MS determination of 4-methylpyrazole in dog plasma and its
           application to a pharmacokinetic study in dogs
    • Authors: Devaraj V. Chandrasekhar; Suresh P. S, Sreekanth Dittakavi, Rakesh A. Hiremath, Ravi Kanth Bhamidipati, Wolfgang Richter, Nuggehally R. Srinivas, Ramesh Mullangi
      Abstract: A simple, specific, sensitive and rapid LC-ESI-MS/MS method has been developed and validated for the quantification of 4-methylpyrazole in dog plasma using N-methylnicotinamide-d4 as an internal standard (IS) as per regulatory guideline.s Sample preparation was accomplished through a simple protein precipitation. Chromatographic separation of 4-methylpyrazole and the IS was performed on a monolithic (Chromolith RP-18e) column using an isocratic mobile phase comprising 0.2% formic acid in water and acetonitrile (20:80, v/v) at a flow rate of 1.0 mL/min. Elution of 4-methylpyrazole and the IS occurred at ~1.60 and 1.56 min, respectively. The total chromatographic run time was 3.2 min. A linear response function was established in the concentration range of 4.96-4955 ng/mL. The intra- and inter-day accuracy and precision were in the range of 1.81-12.9 and 3.80-11.1%, respectively. This novel method has been applied to a pharmacokinetic study in dogs.
      PubDate: 2017-08-15T11:50:24.743575-05:
      DOI: 10.1002/bmc.4065
  • Versatile chromatographic method for catechin determination in development
           of topical formulations containing natural extracts
    • Authors: Ricardo Ferreira-Nunes; Tamara Angelo, Sandra Márcia Mazutti Silva, Pérola Oliveira Magalhães, Tais Gratieri, Marcílio Sérgio Soares Cunha-Filho, Guilherme Martins Gelfuso
      Abstract: Catechin is found in several natural sources, as Eugenia dysenterica and Syzygium cumini extracts. Its antioxidant and UV-protective properties suggest a potential use in cosmetic and dermatological formulations. A simple analytical method capable of giving support to experiments performed along the development of topical formulations containing this natural substance (i.e., drug assay, skin permeation and stability studies), however, is still demanded. Thus, this work aimed to develop and validate a selective HPLC method for catechin determination during the development of topical formulations. Separation was achieved using a RP-C18 column (300 x 3.9 mm; 10 μm), with a mobile phase of methanol/phosphoric acid 0.01 M (15: 85, v/v), flow rate of 0.8 mL/min, temperature set at 40°C, and UV detection at 230 nm. Method was linear in a range from 0.5 to 10.0 μg/mL (r = 0.9998); precise with an overall variation coefficient of 5.5% and accurate with catechin recovery from the skin layers higher than 85%. Additionally, the method was sensitive (limit of detection = 0.109 μg/mL, limit of quantification = 0.342 μg/mL) and selective against plant extracts, skin matrices and formulation interferents, as well as catechin degradation products. It was also robust regarding both methodology parameters and analytical stability.
      PubDate: 2017-08-15T00:35:24.191962-05:
      DOI: 10.1002/bmc.4062
  • Sensitive liquid chromatography/tandem mass spectrometry method for the
           determination of two novel highly lipophilic anti-cancer drug candidates
           in rat plasma and tissues
    • Authors: Shirin Hooshfar; Michael R. Linzey, Daqing Wu, Lajos Gera, Kenza Mamouni, Xin Li, Yanhua Chen, Yang Yang, Oluwasegun Olorunyolemi, Michael G. Bartlett
      Abstract: A simple and sensitive liquid chromatography/electrospray ionization tandem mass spectrometry (LC–ESI-MS/MS) method was developed and validated for determination of two highly lipophilic anti-cancer drug candidates, LG1980, and GH501, in rat plasma and tissues (liver, kidney and femur bones).LG1980 and GH501 were extracted from rat plasma and tissue homogenates using liquid–liquid extraction. The method provided a linear range of 1.0–200.0 ng/mL for GH501 in plasma and LG1980 in plasma and liver. For both analytes in other tissue homogenates the linear range was 2.0-400.0 ng/mL. The method was validated with precision within 15% relative standard deviation (RSD), accuracy within 15% relative error (RE) and a consistent recovery. This method has been successfully applied in two preclinical studies for LG1980 and GH501 to determine their concentrations in rat plasma, liver, kidney and bone over 24 h after intravenous injection of compounds.
      PubDate: 2017-08-12T01:55:19.730529-05:
      DOI: 10.1002/bmc.4064
  • A proteomics method using immunoaffinity fluorogenic derivatization-liquid
           chromatography/tandem mass spectrometry (FD-LC-MS/MS) to identify a set of
           interacting proteins
    • Authors: Katsunori Nakata; Ryoichi Saitoh, Masaki Ishigai, Kazuhiro Imai
      Abstract: Biological functions in organisms are usually controlled by a set of interacting proteins, and identifying the proteins that interact is useful for understanding the mechanism of the functions. Immunoprecipitation is a method that utilizes the affinity of an antibody to isolate and identify the proteins that have interacted in a biological sample. In this study, the FD-LC-MS/MS method, which involves fluorogenic derivatization followed by separation and quantification by HPLC and finally identification of proteins by HPLC-tandem mass spectrometry, was used to identify proteins in immunoprecipitated samples, using Heat shock protein 90 (HSP90) as a model of an interacting protein in HepaRG cells. As a result, HSC70 protein, which was known to form a complex with HSP90, was isolated, together with three different types of HSP90-beta. The results demonstrated that the proposed immunoaffinity-FD-LC-MS/MS method could be useful for simultaneously detecting and identifying the proteins that interact with a certain protein.
      PubDate: 2017-08-12T01:10:37.545287-05:
      DOI: 10.1002/bmc.4063
  • Pharmacokinetics and metabolism of olerciamide A from Portulaca oleracea
           L. in rats by UHPLC-UV and UHPLC-ESI-Q-TOF/MS
    • Authors: Zheming Ying; Cuiyu Li, Mingzhe Gao, Xixiang Ying, Guanlin Yang
      Abstract: The aim of this study was to elucidate the pharmacokinetics of olerciamide A in rats after oral and intravenous administration of P. oleracea L. extract (POE) by a simple and rapid ultra high-performance liquid chromatography (UHPLC) method with bergapten as internal standard (IS). The pharmacokinetic results indicated that olerciamide A was rapidly distributed with Tmax of 30 min after oral administration and presented a low oral absolute bioavailability to be 4.57 %. The metabolism of olerciamide A in rats was also investigated using ultra-high performance liquid chromatography electrospray coupled with quadrupole-time of flight mass spectrometry (UHPLC-ESI-Q-TOF/MS) to elucidate the reason of the low absolute bioavailability of olerciamide A and 7 metabolites of oleraciamide A were found in rat plasma and urine.
      PubDate: 2017-08-12T00:55:24.096787-05:
      DOI: 10.1002/bmc.4061
  • Identification of the constituents and metabolites in rats after oral
           administration of Zi Shen Formula by UPLC-Q-TOF/MS combined pattern
           recognition analysis
    • Authors: Yanchao Zheng; Yidan Zhang, Shihan Geng, Mengxi Xu, Qingshen Yin, Lili Song, Pengwei Zhuang, Yanjun Zhang
      Abstract: An ultra high-performance liquid chromatography mass spectrometry method was established to detect and identify the chemical constituents of Zi Shen Formula (ZSF) and its metabolites in serum, urine and feces, after oral administration into rats. A total of 68 compounds were characterized in ZSF extracts. In vivo, 38 prototype components and 32 metabolites of ZSF were tentatively identified in rat serum, urine and feces. 7 metabolic pathways including demethylation, hydroxylation, oxidation, sulfation, glucuronidation, methylation, de-caffeoyl were proposed to involve in the generation of these metabolites. It was found that glucuronidation, methylation and demethylation were the major metabolic processes of alkaloids, while demethylation, methylation, sulfation and de-caffeoyl were the major metabolic pathways of Phenylethanoid glycosides(PhGs). The main metabolic pathways of steroidal saponins were oxidation and isotype reactions. These findings are significant for our understanding of the metabolism of ZSF. The results proposed metabolic pathways of bioactive components might be crucial for further studies of the mechanisms of action and pharmacokinetic evaluations of ZSF.
      PubDate: 2017-08-09T12:50:23.669034-05:
      DOI: 10.1002/bmc.4060
  • Qualitative Analysis of Psoraleae Fructus by HPLC-DAD/TOF-MS Fingerprint
           and Quantitative Analysis of Multi-components by Single Marker
    • Authors: Lianjun Luan; Xiaoyu Shen, Xuesong Liu, Yongjiang Wu, ManliangTan
      Abstract: A variety of bioactive substances may account for the recognized efficacy and wide clinical application of Psoraleae Fructus in China. A high performance liquid chromatography-diode array detector (HPLC-DAD) fingerprint method was developed to present the comprehensive phytochemical profile of the crude drug. Thirteen major compounds were separated and identified by high performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC/TOF-MS), namely psoralenoside (PO), isopsoralenoside (IPO), psoralen (PS), isopsoralen (IPS), neobavaisoflavone (NBF), bavachin (BC), corylin (CN), bavachromene (BCM), psoralidin (PD), isobavachalcone (IBC), bacachinin (BCN), corylifol A (CA), bakuchiol (BK). Then quantitative analysis of multi-components by single marker (QAMS) was applied in content determination of PO, IPO, PS, IPS, BC, IBC, BCN, CA and BK, with NBF as the internal standard. The calculation results indicated no significant difference with that by the traditional external standard method (P>0.05, RSD
      PubDate: 2017-08-04T14:40:27.736073-05:
      DOI: 10.1002/bmc.4059
  • Study of gliquidone degradation behavior by high-performance thin-layer
           chromatography and ultra-performance liquid chromatography methods
    • Authors: Nada S. Abdelwahab; Mohammed T. Elsaady, Aml G. Korany, Maha A. Hegazy
      Abstract: Gliquidone (GQ) is an oral hypoglycemic agent, belonging to second-generation sulfonylurea derivatives. New high-performance thin-layer chromatography (HPTLC) and ultra-performance liquid chromatography (UPLC) methods have been developed and validated and used for complete stability study of GQ following International Conference on Harmonization guidelines. GQ was subjected to stress and forced degradation under hydrolytic, oxidative and photolytic conditions. The drug was found to be unstable under acidic, alkaline and oxidative conditions with the formation of gliquidone sulfonamide (GQS), while a marked stability was confirmed under thermal and photolytic stress conditions. GQS is the British pharmacopeial impurity A of GQ and also considered as its synthesis intermediate. The developed chromatographic methods have been utilized for anticipating the degradation behavior of GQ under the studied conditions and then used for quantitation of GQ and GQS either in their pure forms or in laboratory prepared mixtures. The methods were successfully applied to GQ in pharmaceutical formulation. The methods have the advantages of being sensitive and less time consuming compared with the reported methods. The obtained results were statistically compared with a reported HPLC method showing no significant difference regarding both accuracy and precision.
      PubDate: 2017-08-03T20:05:40.275508-05:
      DOI: 10.1002/bmc.4025
  • High-performance liquid chromatography–tandem mass spectrometry for
           simultaneous determination of raltegravir, dolutegravir, and elvitegravir
           concentrations in human plasma and cerebrospinal fluid samples
    • Authors: Kiyoto Tsuchiya; Mayu Ohuchi, Naoe Yamane, Hiroaki Aikawa, Hiroyuki Gatanaga, Shinichi Oka, Akinobu Hamada
      Abstract: A simple sample treatment procedure and sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) method were developed for the simultaneous quantification of the concentrations of human immunodeficiency virus-1 (HIV-1) integrase strand transfer inhibitors (INSTIs); raltegravir (RAL), dolutegravir (DTG), and elvitegravir (EVG); in human plasma and cerebrospinal fluid (CSF). Plasma and CSF samples (20 μL each) were deproteinized with acetonitrile. Raltegravir-d3 was used as the internal standard (IS). Chromatographic separation was achieved on an XBridge C18 column (50 mm × 2.1 mm i.d., particle size 3.5 μm) using acetonitrile/water (7:3, v/v) containing 0.1% formic acid as the mobile phase at a flow rate of 0.2 mL/min. The run time was 5 min. Calibration curves for all three drugs were linear in the range 5–1500 ng/mL for plasma and 1–200 ng/mL for CSF. The intra- and inter-day precision and accuracy of all three drugs in plasma were coefficient of variation (CV)
      PubDate: 2017-07-31T20:00:36.077881-05:
      DOI: 10.1002/bmc.4058
  • Multi-components determination of traditional Chinese medicine preparation
           Yin-zhi-huang injection by LC-MS/MS for screening of its potential
           bioactive candidates using HepaRG cells
    • Authors: Zhi Rao; Fan Zhang, Xiao-yi Zhang, Guo-qiang Zhang, Yan-rong Ma, Yan Zhou, Hong-yan Qin, Xin-an Wu, Yu-hui Wei
      Abstract: Yin-zhi-huang (YZH) injection is an injectable multi-herbal prescription derived from the ancient Chinese medicine formula of Yin-chen-hao-tang, which is widely used in the clinic for the treatment of jaundice and chronic liver diseases. To date, the systematic study of the components in this multi-herbal prescription is still challenged by desirable analytical methods, by which a big array of components could be simultaneously detected at low concentrations. Herein, a new liquid chromatography- tandem mass spectrometry (LC-MS/MS) method by using dynamic multiple reaction monitoring (DMRM) mode was developed to determine multiple peaks in traditional Chinese medicine (TCM) preparation YZH injection. This simple, selective and sensitive method enabled the quantification of 22 components with standard materials with the lower limit of quantification (LLOQ) of 1.46-12.5 ng/mL in cell lysates. This method was successfully applied to celluar uptake and/or binding investigation of components in YZH injection. The results indicated that this strategy might be a useful approach for rapidly screening of the potential bioactive candidates from YZH injection, and the discovered candidates would be used to investigate the pharmacodynamics in the further study.
      PubDate: 2017-07-29T09:05:57.134009-05:
      DOI: 10.1002/bmc.4057
  • sQuantification of free fatty acids in human stratum corneum using tandem
           mass spectrometry and surrogate analyte approach
    • Authors: Irena Dapic; Renata Kobetic, Lidija Brkljacic, Sanja Kezic, Ivone Jakasa
      Abstract: The free fatty acids (FFAs) are one of the major components of the lipids in the stratum corneum (SC), the uppermost layer of the skin. Relative composition of FFAs has been proposed as a biomarker of the skin barrier status in patients with atopic dermatitis (AD). Here, we developed LC-ESI-MS/MS method for simultaneous quantification of a range of FFAs with long and very-long chain length in the SC collected by an adhesive tape (D-Squame). Method based on derivatization with 2-bromo-1-methylpyridinium iodide (BMP) and 3-carbinol-1-methylpyridinium iodide (CMP) allowed highly sensitive detection and quantification of FFAs using multiple reaction monitoring (MRM). For the quantification, we applied a surrogate analyte approach and internal standardization using isotope labeled derivatives of FFAs. Adhesive tapes showed presence of several FFAs, which are also present in the SC, a problem encountered in previous studies. Therefore, the levels of FFAs in the SC were corrected by using C12:0 which was present on the adhesive tape, but not detected in the SC. Method was applied on the SC samples of patients with AD and healthy subjects. Quantification using MRM allowed sufficient sensitivity to analyze FFAs of chain lengths C16-C28 in the SC collected in only one tape strip.
      PubDate: 2017-07-29T00:35:25.836762-05:
      DOI: 10.1002/bmc.4056
  • Simultaneous determination of ginsenoside Rb1, ginsenoside Rg1,
           paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma by liquid
           chromatography–tandem mass spectrometry: Application to a
           pharmacokinetic study of wen-Yang-Huo-Xue soft capsule
    • Authors: Xiujun Wu; Yang You, Gonglin Qu, Ran Ma, Mingxue Zhang
      Abstract: A simple and sensitive HPLC–MS/MS method was developed and fully validated for simultaneous determination of ginsenoside Rb1, ginsenoside Rg1, paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma. Plasma samples were pretreated with protein precipitation using acetonitrile. The chromatographic separation was carried out on a C18 column with a gradient mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). All analytes and digoxin (internal stand, IS) were quantitated through electrospray ionization in negative ion multiple reaction monitoring mode. All calibration curves exhibited good linearity (r > 0.9960) over a wide concentration range for all components. The intra-day and inter-day precisions (RSD) at three different levels were all
      PubDate: 2017-07-26T21:26:22.427615-05:
      DOI: 10.1002/bmc.4019
  • Development and validation of an LC-MS/MS method for the simultaneous
           quantification of seven constituents in rat plasma and application in a
           pharmacokinetic study of the Zaoren Anshen prescription
    • Authors: Ajing Zhao; Li Zhang, Rong Li, Jiao Shang, Huihui Yi, Yuan Wang, Dian Zhang, Shixiang Wang, Minfeng Fang
      Abstract: A sensitive, specific and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of seven constituents of the Zaoren Anshen prescription (ZAP) in rat plasma after oral administration of the ZAP: spinosin, salvianic acid A, 6”’-feruloylspinosin, protocatechualdehyde, salvianolic acid B, schisandrin and deoxyschisandrin. The plasma samples and the internal standard (IS) sulfamethoxazole were extracted using acetonitrile. Chromatographic separation was performed with an Agilent HC-C18 column using a gradient elution profile and a mobile phase consisting of 0.01% formic acid in water (A) and acetonitrile (B). The analytes were quantified simultaneously in a single run using an ion trap mass spectrometer operated in the multiple reaction monitoring (MRM) mode and electrospray ion-source polarity in the positive and negative modes. The calibration curves for spinosin, salvianic acid A, 6”’-feruloylspinosin, protocatechualdehyde, salvianolic acid B, schisandrin and deoxyschisandrin were linear over the concentration ranges of 2.90-1160, 2.50-1000, 1.80-720, 0.65-260, 2.50-1000, 8.00-1600 and 1.30-520 ng/mL, respectively. The intra- and inter-day precisions in terms of relative standard deviation were less than 18.9%, and the accuracies in terms of relative error were within ±14.2%. Consequently, the proposed method was successfully applied to the pharmacokinetic analysis of these seven major active compounds in rats administered ZAP. These results will facilitate research aiming to predict the effectiveness of the optimal dose of ZAP and might be beneficial for the therapeutic use of ZAP in the clinical setting.
      PubDate: 2017-07-26T00:50:57.347327-05:
      DOI: 10.1002/bmc.4055
  • Quantitative determination of trigonelline in mice serum by means of
           hydrophilic interaction liquid chromatography-MS/MS analysis –
           application to a pharmacokinetic study
    • Authors: Damian Szczesny; Ewa Bartosińska, Julia Jacyna, Małgorzata Patejko, Danuta Siluk, Roman Kaliszan
      Abstract: Trigonelline (TRG) is a pyridine alkaloid found in fenugreek seeds and coffee beans. Most of the previous studies are concerning quantification of trigonelline along with other constituents in coffee herbs or beverages. Only a few are focused on its determination in animal or human tissues by applying different modes of HPLC with UV or MS detection. The aim of the study was to develop and validate fast and simple method for trigonelline determination in serum by use of hydrophilic interaction liquid chromatography with ESI-MS/MS detection. Separation of trigonelline was achieved on Kinetex HILIC column operated in 35°C with acetonitrile/ammonium formate (10 mM, pH = 3) buffer mixture (55:45, v/v) as the mobile phase. Developed method was successfully applied to determine trigonelline concentration in mice serum after intravenous administration of 10 mg/kg. The developed assay is sensitive (limit of detection = 1.5 ng/ml, limit of quantification = 5.0 ng/ml) and linear in concentration range from 5.0 to 250.0 ng/ml. Sample preparation is limited to deproteinization, centrifugation and filtration. The application of HILIC mode of chromatography with MS detection and selection of deuterated trigonelline as internal standard allowed to develop rapid and precise method of trigonelline quantification.
      PubDate: 2017-07-25T23:30:22.277162-05:
      DOI: 10.1002/bmc.4054
  • Enantioselective determination of R-(−)-manidipine and S-(+)-manidipine
           in human plasma by a sensitive and selective chiral LC–MS/MS assay
    • Authors: Vinayender Adireddy; Bhavani Prasanna Kumar Bimireddy, Venkateswarlu Ponneri
      Abstract: A sensitive and selective liquid chromatography–tandem mass spectrometric (LC–MS/MS) assay method has been developed and validated for the enantioselective determination of manidipine in human plasma using isotope-labeled compounds as internal standards. After solid-phase extraction, R-(−)-manidipine and S-(+)-manidipine were chromatographed on a Chiralpack IC-3 C18 column using a isocratic mobile phase composed of 2 mm ammonium bicarbonate and acetonitrile (15:85, v/v). The precursor ion to product ion transitions for the enantiomers and internal standards were monitored in the multiple reaction monitoring and positive ionization mode using an API-4000 mass spectrometer. The method was linear over the concentration range of 0.05–10.2 ng/mL for both enantiomers. The precision and accuracy results over five concentration levels in five different batches were well within the acceptance limits. The mean extraction recovery was>80% for both enantiomers. A variety of stability tests were executed in plasma and in neat samples, which complies with the FDA guidelines. After complete validation, the method was successfully applied to a pharmacokinetic study of a manidipine 20 mg oral dose in 10 healthy South India subjects under fasting conditions. The assay reproducibility is shown through incurred samples reanalysis of 20 subject plasma samples.
      PubDate: 2017-07-25T17:31:02.337661-05:
      DOI: 10.1002/bmc.4027
  • Residual dynamic and risk assessment of dimethomorph in Swiss chard grown
           in two different sites
    • Authors: Md. Humayun Kabir; A.M. Abd El-Aty, Md. Musfiqur Rahman, Hyung Suk Chung, Han Sol Lee, Mi-Ra Kim, Byung-Joon Chang, Jing Wang, Ho-Chul Shin, Jae-Han Shim
      Abstract: Residue analysis of dimethomorph in Swiss chard cultivated at two different locations under greenhouse conditions was conducted using high-performance liquid chromatography-ultraviolet detector (HPLC-UVD) and confirmed by tandem mass spectrometry (LC-MS/MS). The randomly collected samples (over 14 days) were extracted with acetonitrile and purified using a Florisil solid-phase extraction (SPE) cartridge. Linearity over a concentration range of 0.05–50.0 mg/L had an excellent coefficient of determination (R2) = 0.9996. Recovery rate ranged from 82.98 to 95.43% with relative standard deviations (RSDs) ≤ 5.12%, and limits of detection (LOD) and quantification (LOQ) were 0.003 and 0.01 mg/kg, respectively. The initial deposits (zero day [2-h post-application]) were considerably lower (7.57 and 8.55 mg/kg for Sites 1 and 2, respectively) than the maximum residue limit (MRL = 30 mg/kg) set by the Korean Ministry of Food and Drug Safety. The dissipation half-life was approximately the same, being 5.0 and 5.1 days for Sites 1 and 2, respectively. Risk assessment estimated as acceptable daily intake (ADI%) revealed a value of 0.084 or 0.094% (zero day) and 0.014% (10-days post-application), for Sites 1 and 2, respectively. The values indicated that dimethomorph could be safely used on Swiss chard, with no hazardous effects expected for Korean consumers.
      PubDate: 2017-07-21T08:55:41.749416-05:
      DOI: 10.1002/bmc.4053
  • Quantitative bioanalysis of bavachalcone in rat plasma by LC–MS/MS and
           its application in a pharmacokinetics study
    • Authors: Dan Zhou; Lianhua An, Yan Xia, Yuanyi Wang, Xingliang Li
      Abstract: This study aims to develop and validate a simple and sensitive liquid chromatography with tandem mass spectrometry (LC–MS/MS) method for investigating the pharmacokinetic characteristics of bavachalcone. Liquid–liquid extraction was used to prepare plasma sample. Chromatographic separation of bavachalcone and IS was achieved using a Venusil ASB C18 (2.1 × 50 mm, 5 μm) column with a mobile phase of methanol (A)–water (B) (70:30, v/v). The detection and quantification of analytes was performed in selected-reaction monitoring mode using precursor product ion combinations of m/z 323.1  203.2 for bavachalcone, and m/z 373.0  179.0 for IS. Linear calibration plots were achieved in the range of 1–1000 ng/mL for bavachalcone (r2 > 0.99) in rat plasma. The recovery of bavachalcone ranged from 84.1 to 87.0%. The method was precise, accurate and reliable. It was fully validated and successfully applied to pharmacokinetic study of bavachalcone.
      PubDate: 2017-07-20T00:11:49.633692-05:
      DOI: 10.1002/bmc.4031
  • Simultaneous determination and method validation of difenoconazole,
           propiconazole and pyraclostrobin in pepper and soil by LC−MS/MS in field
           trial samples from three provinces, China
    • Authors: Kunming Zheng; Banghua Meng, Sizhuo Wu, Haizhen Zhang, Fei Wang, Ying Cui, Song Zeng, Kankan Zhang, Deyu Hu
      Abstract: A liquid chromatography-electrospray ionization tandem mass spectrometry method was developed for simple and accurate detection of the fungicides difenoconazole, propiconazole and pyraclostrobin in peppers and soil. Three fungicides residues were extracted from samples by acetonitrile, cleaned up by dispersive solid phase extraction before instrumental analysis. The accuracy and precision of the method were evaluated by conducting intra- and inter-day recovery experiment. The limits of quantification and detection of difenoconazole, propiconazole and pyraclostrobin in pepper and soil were 0.005 and 0.0015 mg/kg, respectively. The recoveries were investigated by spiking pepper and soil at three levels, and were found to range from 79.62% to 103.15% for difenoconazole, 85.94% to 103.35% for propiconazole, and 80.14% to 97.69% for pyraclostrobin, with relative standard deviations below 6.5%. Field experiments were conducted in three locations in China. The half-lives of difenoconazole, propiconazole and pyraclostrobin were 5.3–11.5 days in peppers and 6.1–32.5 days in soil. At harvest, pepper samples were found to contain difenoconazole, propiconazole and pyraclostrobin well below the maximum residue limits of European Union at the interval of 21 days after last application following the recommended dosage.
      PubDate: 2017-07-19T04:50:22.585537-05:
      DOI: 10.1002/bmc.4052
  • Discrimination of Polygoni Multiflori Radix and Cynanchi Auriculati Radix
           using ultra-high performance liquid chromatography fingerprints and
           chemical pattern recognition
    • Authors: Lili Sun; Meng Wang, Yali Liu, Huijie Zhang, Yanan Liu, Xiaoliang Ren, Yanru Deng
      Abstract: In this work, a strategy was proposed to discriminate Polygoni Multiflori Radix (PMR) and its adulteration (Cynanchi Auriculati Radix, CAR). The ultra-high performance liquid chromatography (UHPLC) fingerprints were established to analyze samples containing PMR, CAR and mixtures simultaneously. Multivariate classification methods were applied to analyze the obtained UHPLC fingerprints, including principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), soft independent modeling of class analogy (SIMCA), support vector machine discriminant analysis (SVMDA), and counter-propagation artificial neural network (CP-ANN). A plot of PCA score showed that PMR and CAR samples belonged to separate clusters (PMR class and CAR class), and samples of mixtures were located near PMR or CAR classes. Analysis by PLS-DA, SVMDA and CP-ANN performed well for recognition and prediction in terms of PMR and CAR samples. Moreover, the PLS-DA method performed best in the detection of adulterated samples, even if the adulterant is about 25%.
      PubDate: 2017-07-19T04:40:21.18149-05:0
      DOI: 10.1002/bmc.4050
  • A highly sensitive LC–MS/MS method for simultaneous determination of
           glycyrrhizin and its active metabolite glycyrrhetinic acid: Application to
           a human pharmacokinetic study after oral administration
    • Authors: Tsuneharu Suzuki; Michiko Tsukahara, Yuko Akasaka, Hideo Inoue
      Abstract: A highly sensitive liquid chromatography tandem mass spectrometry (LC–MS/MS) method for simultaneous determination of glycyrrhizin (GL) and its active metabolite, glycyrrhetinic acid (GA), from human plasma was validated and applied to a human pharmacokinetic study. The analytes were extracted from human plasma using an Oasis MAX cartridge and chromatographic separation was performed on an Inertsil ODS-3 column. The detection was performed using an API 4000 mass spectrometer operating in the positive electrospray ionization mode. Selected ion monitoring transitions of m/z 823  453 for GL and m/z 471  149 for GA were obtained. The response was a linear function of concentration over the ranges of 0.5–200 ng/mL for GL and 2–800 ng/mL for GA (both R2 > 0.998). Using this method, the pharmacokinetics of GL after single oral administration of a clinical dose (75 mg) to six healthy male Japanese volunteers were evaluated. GL was detected in the plasma of all subjects and the average peak concentration was 24.8 ± 12.0 ng/mL. In contrast, peak concentration of GA was 200.3 ± 60.3 ng/mL, i.e. ~8-fold higher than that of GL. This is the first report clarifying pharmacokinetic profiles of GL and GA simultaneously at a therapeutic oral dose of a GL preparation.
      PubDate: 2017-07-18T20:30:47.028978-05:
      DOI: 10.1002/bmc.4032
  • Quantification of β-eudesmol in rat plasma using LC–MS/MS and its
           application to a pharmacokinetic study
    • Authors: Ligang Jiang; Chunyang Zhang, Haiping Li
      Abstract: A sensitive and specific LC–MS/MS assay for determination of β-eudesmol in rat plasma was developed and validated. After liquid–liquid extraction with ethyl ether, the analyte and IS were separated on a Capcell Pak C18 column (50 × 2.0 mm, 5 μm) by isocratic elution with acetonitrile—water–formic acid (77.5:22.5:0.1, v/v/v) as the mobile phase at a flow rate of 0.4 mL/min. An ESI source was applied and operated in positive ion mode; a selected reaction monitoring scan was used for quantification by monitoring the precursor–product ion transitions of m/z 245.1  163.1 for β-eudesmol and m/z 273.4  81.2 for IS. Good linearity was observed in the concentration range of 3–900 ng/mL for β-eudesmol in rat plasma. Intra- and inter-day precision and accuracy were both within ±14.3%. This method was applied for pharmacokinetic studies after intravenous bolus of 2.0 mg/kg or intragastric administration of 50 mg/kg β-eudesmol in rats.
      PubDate: 2017-07-18T20:20:51.77754-05:0
      DOI: 10.1002/bmc.4023
  • Chemical UPLC-ESI-MS/MS profiling of aconitum alkaloids and their
           metabolites in rat plasma and urine after oral administration of Aconitum
           carmichaelii Debx. root extract
    • Authors: Mingjie Zhang; Manman Wang, Jiajia Liang, Yongqing Wen, Zhili Xiong
      Abstract: In this paper, an ultra high performance liquid chromatography tandem mass spectrometric (UPLC-ESI-MS/MS) method in positive ion mode was established to systematically identify and to compare the major aconitum alkaloids and their metabolites in rat plasma and urine after oral administration of Fuzi extract.A total twenty-nine components including twenty-five C19-diterpenoid alkaloids and four C20-diterpenoid alkaloids were identified in Fuzi extract. Thirteen of the parent components and five metabolites were detected in rat plasma and sixteen parent compounds and six metabolites in urine. These parent components found in rat plasma and urine were mainly C19-diterpenoid alkaloids.All of the metabolites in vivo were demethylated metabolites (phase I metabolites), which suggested that demethylation was the major metabolic pathway of aconitum alkaloids in vivo. A comparison of the parent components in rat plasma and urine revealed that 3-deoxyacontine was found in plasma but not in urine, while kalacolidine, senbusine and 16-β-hydroxycardiopetaline existed in urine but not in plasma, which indicated that most alkaloids components were disposed and excreted in prototype form. This research provides some important information for further metabolic investigations of Fuzi in vivo.
      PubDate: 2017-07-18T03:20:54.699557-05:
      DOI: 10.1002/bmc.4049
  • Metabolomics revealed the toxicity of cationic liposomes in HepG2 cells
           using UHPLC-Q-TOF/MS and multivariate data analysis
    • Authors: Jing Yu; Hai Zhang, Ying Li, Sen Sun, Jie Gao, Yanqiang Zhong, Duxin Sun, Guoqing Zhang
      Abstract: Cationic liposomes (CLs) are novel nonviral vectors widely used for delivering drugs or genes. However, applications of CLs are largely hampered by their cytotoxicity, partly because the potential mechanism underlying the cytotoxicity of CLs remains unclear. The aim of the present study was to explore the underlying mechanism of cytotoxicity induced by CLs on HepG2 cells. Differential metabolites were identified and quantified using ultra-liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). The toxicity of CLs on HepG2 cells was evaluated by multivariate data analysis and statistics. Additionally, CCK-8 assay, heatmap, pathway and co-expression network were carried out to explore the relations between the metabolites and the pathways. The results showed a dose-dependent toxic effect of CLs on HepG2 cells, with an IC50 value of 119.9 μg/mL. Multivariate statistical analysis identified 42 potential metabolites between CLs exposure and control groups. Pathway analysis showed significant changes in pathways involving amino acid metabolism, energy metabolism, lipid metabolism and oxidative stress in the CLs exposure group vs the control group. Metabolites related to the above-mentioned pathways included phenylalanine, methionine, creatine, oxalacetic acid, glutathione, oxidized glutathione, choline phosphate and several unsaturated fatty acids, indicating that cells were disturbed in amino acid metabolism, energy and lipid supply when CLs exposure-induced injury occurred. It is concluded that CLs may induce cytotoxicity by enhancing reactive oxygen species in vitro, affect the normal process of energy metabolism, disturb several vital signaling pathways and finally induce cell death.
      PubDate: 2017-07-17T21:10:59.393126-05:
      DOI: 10.1002/bmc.4036
  • Pharmacokinetic comparison of two phenolic acids after oral administration
           of Typhae pollen to normal rats and rats with acute cold blood stasis
    • Authors: Yingni Pan; Wenjie Zhang, Wei Zhang, Xuewei Bai, Shumeng Ren, Jiang Zheng, Dongmei Wang, Xiaoqiu Liu
      Abstract: Typhae Pollen, dried pollen of Typha angustifolia L., Typha orientalis Presl or other plants of the same genus (Typhaeceae), has the effect of activating the circulation to cure blood stasis in traditional Chinese Medicine. The purpose of this study was to set up an ultra-high performance liquid chromatography method that could determine p-hydroxybenzoic acid and vanillic acid simultaneously in rat plasma, and to compare their pharmacokinetics in normal rats and rats with acute cold blood stasis, and further to investigate the influence of different dosages of oral administration. The pharmacokinetic parameters obtained showed that both of the phenolic acids had a higher bioavailability in rats with cold blood stasis than that in normal rats with a higher area under the concentration–time curve and longer mean residence time, and the high dose oral administration group had a higher capacity in blood stasis rats than in normal rats. These results reminded us that changes in health condition could alter the absorption and elimination of both phenolic acids in vivo, and the pharmacokinetic study under pathological conditions provides important information for more rational drug use in clinical situations.
      PubDate: 2017-07-16T21:00:30.888381-05:
      DOI: 10.1002/bmc.4028
  • Lansoprazole-sulfide, pharmacokinetics of this promising anti-tuberculous
    • Authors: Sipho Mdanda; Sooraj Baijnath, Adeola Shobo, Sanil D. Singh, Glenn E.M. Maguire, Hendrik G. Kruger, Per I. Arvidsson, Tricia Naicker, Thavendran Govender
      Abstract: Lansoprazole (LPZ) is a commercially available proton-pump inhibitor whose primary metabolite, lansoprazole sulfide (LPZS) was recently reported to have in vitro and in vivo activity against Mycobacterium tuberculosis. It was also reported that a 300 mg kg−1 oral administration of LPZS was necessary to reach therapeutic levels in the lung, with the equivalent human dose being unrealistic. A validated liquid chromatography–tandem mass spectrometric method (LC–MS/MS) for the simultaneous quantification LPZ and LPZS in rat plasma and lung homogenates was developed. We administered 15 mg kg−1 oral doses of LPZ to a healthy rat model to determine the pharmacokinetics of its active metabolite, LPZS, in plasma and lung tissue. We found that the LPZS was present in amounts that were below the limit of quantification. This prompted us to administer the same dose of LPZS to the experimental animals intraperitoneally (i.p.). Using this approach, we found high concentrations of LPZS in plasma and lung, 7841.1 and 9761.2 ng mL−1, respectively, which were significantly greater than the minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis. While oral and i.p. administration of LPZ resulted in significant concentrations in the lung, it did not undergo sufficient cellular conversion to its anti-TB metabolite. However, when LPZS itself was administered i.p., significant amounts penetrated the tissue. These results have implications for future in vivo studies exploring the potential of LPZS as an anti-TB compound.
      PubDate: 2017-07-13T20:55:57.911315-05:
      DOI: 10.1002/bmc.4035
  • Screening and identification of metabolites of two kinds of main active
           ingredients and hepatotoxic pyrrolizidine alkaloids (HPAs) in rat after
           lavage Farfarae Flos extract by UHPLC-Q-TOF-MS mass spectrometry
    • Authors: Xiaoye Cheng; Man Liao, Xinpeng Diao, Yupeng Sun, Lantong Zhang
      Abstract: Farfarae Flos, the dried flower buds of Tussilago farfara L., is usually used to treat coughs, bronchitic and asthmatic conditions as an important traditional Chinese medicine. Tussilagone and methl butyric acid tussilagin ester are seen as representatives of two kinds of active substances. Besides, the pyrrolizidine alkaloids (HPAs), mainly senkirkine and senecionine, presented in the herb can be hepatoxic. In this study, a rapid and sensitive ultra high performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) method is successfully applied to identify the metabolites of tussilagone, methl butyric acid tussilagin ester , senkirkine and senecionine. The results showed that a total of 35, 37, 18 and 9 metabolites of tussilagone, methl butyric acid tussilagin ester, senkirkine and senecionine in rats were tentatively identified. Hydrolysis, oxidation, reduction and demethylation were the major metabolic reactions for tussilagone and methl butyric acid tussilagin ester. The main biotransformation routes of senkirkine and senecionine were identified as demethylation, N-methylation, oxidation and reduction. This study is the first reported analysis and characterization of the metabolites and the proposed metabolic pathways might provide further understanding of the metabolic fate of the chemical constituents after oral administration of Farfarae Flos extract in vivo.
      PubDate: 2017-07-12T20:00:26.338401-05:
      DOI: 10.1002/bmc.4047
  • LC–MS/MS characterization, anti-inflammatory effects and antioxidant
           activities of polyphenols from different tissues of Korean Petasites
           japonicus (Meowi)
    • Authors: Jin Young Choi; Kebede Taye Desta, Venu Venkatarame Gowda Saralamma, Sung Joong Lee, Soo Jung Lee, Seong Min Kim, Anjugam Paramanantham, Ho Jeong Lee, Yun-Hi Kim, Ho-Chul Shin, Jae-Han Shim, Mohamad Warda, Ahmet Hacımüftüoğlu, Ji Hoon Jeong, Sung Chul Shin, Gon-Sup Kim, A. M. Abd El-Aty
      Abstract: The Korean Petasites japonicus is a perennial plant used in folk medicine as a remedy for many diseases and popularly consumed as spring greens. Ten polyphenols were characterized from the leaves, stems and roots of this plant via high-performance liquid chromatography–tandem mass spectrometry. Individual polyphenols were quantified for the first time using calibration curves of six structurally related external standards. Validation data indicated that coefficients of determinations (R2) were ≥0.9702 for all standards. Recoveries measured at 50 and 100 mg/L were 80.0–91.9 and 80.3–105.3%, respectively. Precisions at these two concentration levels were 0.7–6.1 and 1.1–5.5%, respectively. The total number of identified components was largest for the leaves and smallest for the stems. The leaf and root polyphenolic extracts showed anti-inflammatory effects by inducing LPS-activated COX-2 and iNOS protein levels in mouse macrophage RAW 264.7 cells. The antioxidant capacity of the polyphenols, when evaluated for DPPH (α,α-diphenyl-β-picrylhydrazyl)ˑ, ABTS+ [2–2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] and superoxide radical scavenging activities, and in ferric reducing ability of plasma (FRAP) assays, was highest in the leaf and lowest in the stem. This trend suggests that the antioxidant capacities depend primarily on polyphenol concentration in each tissue. The current findings suggest that polyphenols derived from P. japonicas tissues could have potential as functional health foods.
      PubDate: 2017-07-11T21:01:01.098259-05:
      DOI: 10.1002/bmc.4033
  • Fast ultra-high-performance liquid chromatography with diode array and
           mass spectrometry method for determination of tadalafil drug substance and
           its impurities
    • Authors: Ludovit Schreiber; Radoslav Halko, Milan Hutta
      Abstract: Tadalafil is used for the treatment of erectile dysfunction. Its related patents expired in 2016, and so related generic drug production is predicted to be increased. This work is focused on developing a fast ultra-high-performance liquid chromatography with diode array detection and/or mass spectrometry detection for the separation and determination of tadalafil and its impurities in pharmaceutical samples. A modern reversed-phase stationary phase with sub-2 μm particle size, Zorbax StableBond Rapid Resolution High Definition with octylsilane chemically bonded phase to totally porous silica particles, was used for the solving this problem. Column temperature was set at 40 ± 0.1°C. A mobile phase consisting of acetonitrile and aqueous solution of 0.1% (v/v) trifluoroacetic acid for diode array detection detection and 0.05% (v/v) formic acid, both running at a flow rate of 0.62 mL/min, were used to achieve the required separation of all components within a 5 min run. The limit of detection was 3.5 μg/L and the limit of quantification was 10.0 μg/L for the method for both UV and MS detectors. Accurate mass spectra of tadalafil's related impurities are shown for advanced confirmation. The method is directly transferable to routine analysis of tadalafil in pharmaceutical and control laboratories.
      PubDate: 2017-07-11T00:15:34.648503-05:
      DOI: 10.1002/bmc.4020
  • Development of a HPLC method for determination of four UV filters in
           sunscreen and its application to skin penetration studies
    • Authors: Carla Souza; Patrícia M.B.G. Maia Campos
      Abstract: This study describes the development, validation and application of a high-performance liquid chromatography (HPLC) method for the simultaneous determination of the in vitro skin penetration profile of four UV filters on porcine skin. Experiments were carried out on a gel-cream formulation containing the following UV filters: diethylamino hydroxybenzoyl hexyl benzoate (DHHB), bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) and ethylhexyl triazone (EHT). The HPLC method demonstrated suitable selectivity, linearity (10.0–50.0 μg/mL), precision, accuracy and recovery from porcine skin and sunscreen formulation. The in vitro skin penetration profile was evaluated using Franz vertical diffusion cells for 24 h after application on porcine ear skin. None of the UV filters penetrated the porcine skin. Most of them stayed on the skin surface (>90%) and only BEMT, EHT and DHHB reached the dermis plus epidermis layer. These results are in agreement with previous results in the literature. Therefore, the analytical method was useful to evaluate the in vitro skin penetration of the UV filters and may help the development of safer and effective sunscreen products.
      PubDate: 2017-07-10T20:05:46.621725-05:
      DOI: 10.1002/bmc.4029
  • A validated UHPLC–MS/MS method for the measurement of riluzole in plasma
           and myocardial tissue samples
    • Authors: Suzanne L. Parker; Yarmarly C. Guerra Valero, Jeffrey Lipman, Steven Weiss, Camilla Smith, Lyndal Russell, Paul Smith, Jason A. Roberts, Steven C. Wallis
      Abstract: Through blocking the cardiac persistent sodium current, riluzole has the potential to prevent myocardial damage post cardiac bypass surgery. A sensitive UHPLC–MS/MS method was developed and validated for quantitation of riluzole and 5-methoxypsoralen in human plasma and myocardial tissue homogenate using a liquid–liquid extraction with dichloromethane. The chromatographic separation was achieved using Shimadzu Shim-pack XR-ODS III, 2.0 × 50 mm, 1.6 μm column with a gradient mobile phase comprising methanol and ammonium acetate buffer pH 3.6 in purified water. The analyte and internal standard were separated within 3.5 min. Riluzole quantitation was achieved using the mass transitions of 235–138 for riluzole and 217–156 for 5-methoxypsoralen. The method was linear for riluzole plasma concentrations from 0.2 to 500 ng/mL and myocardial tissue homogenate concentrations from 0.2 to 100 ng/mL. The method developed was successfully applied to a clinical study for patients receiving riluzole while undergoing cardiac bypass surgery.
      PubDate: 2017-07-10T19:50:29.221011-05:
      DOI: 10.1002/bmc.4030
  • Determination of the serine palmitoyl transferase inhibitor myriocin by
           electrospray and Q-trap mass spectrometry
    • Authors: Giuseppe Matteo Campisi; Paola Signorelli, Jessica Rizzo, Claudio Ghilardi, Jacopo Antognetti, Anna Caretti, Jelena S. Lazarević, Enrica Strettoi, Elena Novelli, Riccardo Ghidoni, Federico Maria Rubino, Rita Paroni
      Abstract: Myriocin is a potent inhibitor of serine-palmitoyl-transferase, the first and rate-determining enzyme in the sphingolipids biosynthetic pathway. This study developed, validated and applied a LC–MS/MS method to measure myriocin in minute specimens of animal tissue. The chemical analog 14-OH–myriocin was used as the internal standard. The two molecules were extracted from the tissue homogenate by solid-phase extraction, separated by gradient reversed-phase liquid chromatography and measured by negative ion electrospray mass spectrometry in the triple quadrupole. Detection was accomplished by multiple reaction monitoring, employing the most representative transitions, 400@104 and 402@104 for myriocin and 14-OH-myriocin, respectively. The typical limit of detection and lower limit of quantitation of the optimized method were 0.9 pmol/mL (~0.016 pmol injected) and 2.3 pmol/mL, respectively, and the method was linear up to 250 pmol/mL range (r2 = 0.9996). The intra- and between-day repeatability afforded a coefficient of variation ≤7.0%. Applications included quantification of myriocin in mouse lungs after 24 h from administration of ~4 nmol by intra-tracheal delivery. Measured levels ranged from 4.11 (median; 2.3–7.4 IQR, n = 4) to 11.7 (median; 7.6–22.7 interquartile range (IQR), n = 6) pmol/lung depending on the different formulations used. Myriocin was also measured in retinas of mice treated by intravitreal injection and ranged from 0.045 (less than the limit of detection) to 0.35 pmol/retina.
      PubDate: 2017-07-10T19:40:34.188989-05:
      DOI: 10.1002/bmc.4026
  • The human mast cell line-1 cell membrane chromatography coupled with
           HPLC-ESI-MS/MS method for screening potentical anaphylactic components
           from chuanxinlian injection
    • Authors: Yuanyuan Lin; Cheng Wang, Yajing Hou, Huaizhen He, Limin Huang, Liu Yang, Meng Sun
      Abstract: Chuanxinlian injection is a traditional Chinese medicine injection widely used in China to treat sore throat, cough and dysentery, although a high occurrence of severe adverse reactions has been reported in clinical practice in recent years. In the present study, a human mast cell line-1 cell membrane chromatography coupled with HPLC-ESI-MS/MS method was established to screen and identify potentical anaphylactic components in chuanxinlian injection, and the dehydroandrographolide was identified as a potential anaphylactic component. In vitro anaphylactic assay showed that intracellular Ca2+ concentration clearly increased under dehydroandrographolide (100 μm) treatment. β-Hexosaminidase and histamine release in human mast cell line-1 cells were both markedly enhanced with increased concentrations of dehydroandrographolide, confirming the anaphylactic activity of dehydroandrographolide. The application for chuanxinlian injection in this study suggested that the developed human mast cell line-1 cell membrane chromatography coupled with HPLC-ESI-MS/MS system may be effective and rapid for screening the potentical anaphylactic components from complex samples.
      PubDate: 2017-07-06T20:40:40.648037-05:
      DOI: 10.1002/bmc.4015
  • Determination of Tigecycline in Human Plasma by LC-MS/MS and its
           Application to Population Pharmacokinetics Study in Chinese Patients with
           Hospital-acquired Pneumonia
    • Authors: Rong Shao; Xingang Li, Yangmin Hu, Jinliang Chen, Honggang Lou, Haibin Dai
      Abstract: A selective, sensitive, and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of Tigecycline (TGC) in human plasma, using Tigecycline-d9 as an internal standard (IS). Analytical samples were prepared using a protein precipitation method coupled with a concentration process. The analyte and IS were separated on a reversed-phase Waters Acquity UPLC® BEH-C18 column (2.1 mm × 50 mm ID, 1.7 μm) with a flow rate of 0.25 ml/min. The mobile phase consisted of water, containing 0.2% formic acid (v/v) with 10 mM ammonium formate (A) and acetonitrile (B). The mass spectrometer was operated in selected reaction monitoring (SRM) mode through electrospray ionization ion mode using the transitions of m/z 586.2513.1 and m/z 595.1514.0 for TGC and IS, respectively. The linearity of the method was in the range of 10-5000 ng/ml. Intra- and inter-batch precision (% CV) for TGC were less than 9.27%, and the accuracy ranged from 90.06% to 107.13%. This method was successfully applied to the analysis of samples from hospital-acquired pneumonia (HAP) patients treated with TGC, and a validated population pharmacokinetic (PPK) model was established. This developed method could be quite useful to predict PK parameters and valuable for further PK/PD studies.
      PubDate: 2017-07-05T06:00:37.167614-05:
      DOI: 10.1002/bmc.4045
  • Development and Validation of a High-Performance Liquid Chromatography
           Method for the Quantification of Talazoparib in Rat Plasma: Application to
           Plasma Protein Binding Studies
    • Authors: Mahendra Kumar Hidau; Srikanth Kolluru, Srinath Palakurthi
      Abstract: A sensitive and selective RP-HPLC method has been developed and validated for the quantification of a highly-potent poly ADP ribose polymerase (PARP) inhibitor talazoparib (TZP) in rat plasma. Chromatographic separation was performed with isocratic elution method. Absorbance for TZP was measured with UV detector (SPD-20A UV-VIS) at λmax of 227 nm. Protein precipitation method was used to extract the drug form plasma samples using methanol: acetonitrile (65:35) as a precipitating solvent. Method was shown sensitive and reproducible over 100-2000 ng/mL linearity range with LLQC of 100 ng/mL. TZP recovery was found to be>85%. Following analytical method development and validation, it was successfully employed to determine the plasma protein binding of TZP. It was found that TZP has high protein binding in rat plasma (95.76 ± 0.38 %) as determined by dialysis method.
      PubDate: 2017-07-05T05:40:19.478367-05:
      DOI: 10.1002/bmc.4046
  • Validated LC-MS/MS method for quantitation of demethylbellidifolin in rat
    • Authors: Jie Zhang; Huiyu Yan, Xiaoyu Qu, Wei Zhou
      Abstract: Demethylbellidifolin, a major xanthone compound of Swertia davidi Franch, showed many beneficial pharmacological effects including antioxidation, anti-inflammation, anti-fibrosis, and cardiovascular protection effects. In this research, a rapid and sensitive LC-MS/MS method for the quantitative analysis of demethylbellidifolin in rat plasma was developed. The demethylbellidifolin and internal standard of aurantio-obtusin were extracted from 50 μL of rat plasma samples with ethyl acetate, then the dried residue was reconstituted and injected in an HPLC system with ZORBAX SB-C18 analytical column (2.1 mm × 100 mm, 3.5 μm) and eluted with the mobile phase consisting of methanol and 0.2% formic acid aqueous solution (80:20, v/v). Quantification was performed by a TSQ QUANTUM ULTRA mass spectrometer in negative ESI using SRM mode of the transitions m/z 259.1215.1 for demethylbellidifolin and 329.0314.2 for the IS. Excellent linearity was observed between 1.92 and 960 ng/mL with a limit of quantitation of 1.92 ng/mL. Intra- and inter-day precision (RSD) values of QC samples were both less than 8.3%. This study was successfully utilized for the pharmacokinetic profiles of demethylbellidifolin in rats after oral or intravenous administration. The oral bioavailability of demethylbellidifolin was determined to be 3.6%.
      PubDate: 2017-07-05T05:00:19.448471-05:
      DOI: 10.1002/bmc.4043
  • A platinized stainless steel fiber with in-situ coated
           polyaniline/polypyrrole/graphene oxide nanocomposite sorbent for headspace
           solid-phase microextraction of aliphatic aldehydes in rice samples
    • Authors: Alireza Ghiasvand; Afagh Nasirian, Samira Koonani, Kolsoum Nouriasl
      Abstract: The surface of a stainless steel fiber was made larger, porous and cohesive by platinizing for tight attachment of its coating. Then it was coated by a polyaniline/polypyrrole/graphene oxide (PANI/PP/GO) nanocomposite film using electrochemical polymerization. The prepared PANI/PP/GO fiber was used for headspace solid-phase microextraction (HS-SPME) of linear aliphatic aldehydes in rice samples followed by GC-FID determination. To achieve the highest extraction efficiency, various experimental parameters including extraction time and temperature, matrix modifier and desorption condition were studied. The linear calibration curves were obtained over the range of 0.05–20 μg g−1 (R2 > 0.99) for C4–C11 aldehydes. The limits of detection were found to be in the range of 0.01–0.04 μg g−1. RSD values were calculated to be
      PubDate: 2017-07-04T23:55:29.355022-05:
      DOI: 10.1002/bmc.4024
  • Metabolic profiling of quercetin in rats using ultra-performance liquid
           chromatography/quadrupole-time-of-flight mass spectrometry
    • Authors: Ming-jiang Wu; Xiao-lei Wu, De-qin Zhang, Feng Qiu, Li-qin Ding, Hao-ling Ma, Xin-ze Chen
      Abstract: Quercetin, a kind of major flavonoid found in many traditional chinese medicines, is an effective substance for treatments such as lowering blood lipids. However, the studies on quercetin have been mainly focused on its pharmacological effect; the treatment of diseases on a material basis, particularly the metabolites derived from quercetin in vivo, has not been evaluated. In this study, we determined the levels, distributions and types of quercetin's metabolites in plasma, urine, feces and bile of rats after a single oral administration of quercetin at a dose of 80 mg/kg, using ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A total of 36 metabolites of quercetin were identified, including 11 metabolites in plasma, 34 metabolites in urine, 12 metabolites in feces and 21 metabolites in bile. The results showed that phase I metabolites were reduction metabolites and phase II metabolites mainly included glucuronidation, sulfation and methylation metabolites. These results provide important information on the metabolism of quercetin, which will be helpful for its further development and utilization.
      PubDate: 2017-07-04T23:40:34.325751-05:
      DOI: 10.1002/bmc.4016
  • Development of a validated UPLC–MS/MS method for determination of
           humantenmine in rat plasma and its application in pharmacokinetics and
           bioavailability studies
    • Authors: Yanxian Hu; Minghao Chen, Zhaoyu Wang, Yao Lan, Lan Tang, Menghua Liu, Jie Zhao, Ming Hu, Lulu Zhang, Ling Ye
      Abstract: Humantenmine (HMT), the most toxic compound isolated from Gelsemium elegans Benth, is a well-known active herbal compound. A rapid and sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and validated to estimate the absolute oral bioavailability of HMT in rats. Quantification was performed by multiple reaction monitoring using electrospray ionization operated in positive ion mode with transitions of m/z 327.14  m/z 296.19 for HMT and m/z 323.20  m/z 236.23 for gelsemine (internal standard, IS). The linear range of the calibration curve was 1–256 nmol/L, with a lower limit of quantification at 1 nmol/L. The accuracy of HMT ranged from 89.39 to 107.5%, and the precision was within 12.24% (RSD). Excellent recovery and negligible matrix effect were observed. HMT remained stable during storage, preparation and analytical procedures. The pharmacokinetics of HMT in rats showed that HMT reached the concentration peak at 12.50 ± 2.74 min with a peak concentration of 28.49 ± 6.65 nmol/L, and the corresponding area under the concentration–time curve (AUC0–t) was 1142.42 ± 202.92 nmol/L min after 200 μg/kg HMT was orally administered to rats. The AUC0–t of HMT given at 20 μg/kg by tail vein administration was 1518.46 ± 192.24 nmol/L min. The calculated absolute bioavailability of HMT was 7.66%.
      PubDate: 2017-07-03T20:06:02.557955-05:
      DOI: 10.1002/bmc.4017
  • Quantification of morusin using LC–MS in rat plasma: Application to
           a pharmacokinetic study
    • Authors: Zhipeng Deng; Xiaohui Sun, Shenbao Yang, Lei Zhang, Peilu Sun, Xuepeng Teng, Hao Zhong
      Abstract: A sensitive LC–MS method was developed for the quantification of morusin in rat plasma using praeruptorin C as internal standard. After extraction with diethyl ether, post-treatment samples were chromatographed on a Hypersil C18 column. An isocratic mobile phase consisting of methanol–water (70:30, v/v) was applied at a flow rate of 0.4 mL/min. Detection was performed via electrospray ionization source with positive ion mode using selected ion monitoring mode at m/z 443.1 for morusin and m/z 451.0 for IS. Acceptable linearity (r2 ≥ 0.99) was observed over the concentration range of 1.5–800 ng/mL. This method was successfully applied in the pharmacokinetics study of morusin in rats.
      PubDate: 2017-06-29T23:35:24.641277-05:
      DOI: 10.1002/bmc.4021
  • Single-step isolation of embelin using high-performance countercurrent
           chromatography and determination of the fatty acid composition of seeds of
           Embelia schimperi
    • Authors: Minaleshewa Atlabachew; Bewketu Mehari, Sandra Combrinck, Robert McCrindle
      Abstract: Embelin (2,5-dihydroxy-3-undecyl-p-benzoquinone) is known for its potent anthelmintic activity, but also for wound-healing, antidiabetic, anticonvulsant, antitumour, anti-inflammatory, analgesic, hepatoprotective, antioxidant, antibacterial and antispermatogenic activities. A high-performance countercurrent chromatography method was developed for the purification of embelin from an extract of the seeds of Embelia schimperi fruit. The optimized solvent system (n-hexane–ethylacetate–ethanol–water, 7:3:7:3) resulted in the isolation of 13.9 mg of embelin, directly from 100 mg of crude extract, in a single step within a short time (40 min). Although the compound appeared to be completely pure when analysed by ultra-performance liquid chromatography (UPLC) with photo diode array detection, the purity was established as ~90% by UPLC–mass spectrometry. Furthermore, we report the fatty acid composition of the seeds of E. schimperi fruit. Nine fatty acids were quantified from the fruit seed extract by gas chromatography–mass spectrometry, with linoleic (46.4%), palmitic (21.5%) and oleic (19.6%) acids making up the largest proportions.
      PubDate: 2017-06-29T19:50:26.286635-05:
      DOI: 10.1002/bmc.4018
  • Hydrophilic interaction and reversed-phase ultra-performance liquid
           chromatography TOF-MS for metabolomic analysis of Veratrum nigrum-induced
    • Authors: Ziheng Wei; Xu Dong, Hanzhe Zhang, Songyan Gao, Wei Shi, Feng Yang, Xin Dong
      Abstract: The acute cardiotoxicity induced by Veratrum nigrum (VN) is explored by analyzing heart tissue metabolic profiles in mouse models and applying reversed-phase liquid chromatography mass spectrometry and hydrophilic interaction liquid chromatography mass spectrometry that are based on ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. An animal model of acute heart injury was established in mice via intra-gastric administration of VN. Then, electrocardiogram and echocardiograph monitoring of cardiac function and pathological examination were performed on mice in both the control and VN groups, and it was verified that acute heart injury was caused. Meanwhile, comparing the results of the control and VN groups, we detected 36 differential endogenous metabolites of heart tissue, including taurine, riboflavin, purine and lipids, which are related to many possible pathways such as purine metabolism, taurine and hypotaurine metabolism and energy metabolism. Our study provides a scientific approach for evaluating and revealing the mechanisms of VN-induced cardiotoxicity via the metabolomic strategy.
      PubDate: 2017-06-29T19:40:55.939417-05:
      DOI: 10.1002/bmc.4011
  • Relationship between the UPLC-Q-TOF-MS fingerprinted constituents from
           Daphne genkwa and their anti-inflammatory, anti-oxidant activities
    • Authors: Wen-Juan Du; Jun Ji, Ling Wang, Xin-Yi Lan, Jia Li, Jun-Qiu Lei, Xin He, Chun-Feng Zhang, Wen-Zhe Huang, Zhen-Zhong Wang, Wei Xiao, Chong-Zhi Wang, Chun-Su Yuan
      Abstract: Daphne genkwa Zucc. is a well-known medicinal plant. This study was designed to apply the ultra-high performance liquid chromatography system to establish a quality control method for D. genkwa. Data revealed that there were 15 common peaks in 10 batches of D. genkwa Sieb. Et Zucc. (Thymelaeaceae) from different provinces of China. On this basis, the fingerprint chromatogram was established to provide references for quality control. Afterwards, the chemical constitutions of these common peaks were analyzed using the UPLC-Q-TOF-MS system and nine of them were identified. In addition, LPS-stimulated RAW264.7 murine macrophages and DPPH assay were used to study the anti-inflammatory and anti-oxidation effects of D. genkwa. Then the fingerprint–efficacy relationships between UPLC fingerprints and pharmacodynamic data were studied with canonical correlation analysis. Analysis results indicated that the anti-inflammatory and anti-oxidation effects differed among the 10 D. genkwa samples owing to their inherent differences of chemical compositions. Taken together, this research established a fingerprint–efficacy relationship model of D. genkwa plant by combining the UPLC analytic technique and pharmacological research, which provided references for the detection of the principal components of traditional Chinese medicine on bioactivity.
      PubDate: 2017-06-20T21:50:42.680506-05:
      DOI: 10.1002/bmc.4012
  • Simultaneous quantification of Imatinib and its main metabolite
           N-demethyl-Imatinib in human plasma by liquid chromatography-tandem mass
           spectrometry and its application to therapeutic drug monitoring in
           patients with gastrointestinal stromal tumor
    • Authors: Wei Zhuang; Hai-bo Qiu, Xin-meng Chen, Xiu-hong Yuan, Li-fang Yang, Xiao-wei Sun, Xiao-jun Zhou, Min Huang, Xue-ding Wang, Zhi-wei Zhou
      Abstract: AimTo improve and validate a more stable and less time-consuming method based on liquid chromatography and tandem mass spectrometry (LC- MS/MS) for the quantitative measurement of Imatinib and its metabolite N-demethyl-Imatinib (NDI) in human plasma.MethodsSeparation of analytes was performed on a Waters XTerra RP18 column (50mm×2.1 mm i.d., 3.5 μm) with a mobile phase consisting of methanol/acetonitrile/ water (65:20:15, v/v/v) with 0.05% formic acid at a flow-rate of 0.2 ml/min. The Quattro MicroTM triple quadruple mass spectrometer was operated in the multiple-reaction monitoring mode via positive electrospray ionization interface using the transition: m/z 494.0 394.0 for Imatinib, m/z 479.6 394.0 for NDI and m/z 488.2 394.0 for IS.ResultsThe method was linear over 0.01–10 μg/mL for Imatinib and NDI. The intra- and inter-day precisions were all less than 15% in terms of relative standard deviation (RSD), and the accuracy was within ±15% in terms of relative error (RE) for both Imatinib and NDI. The lower limit of quantification (LLOQ) was identifiable and reproducible at 10 ng/mL.ConclusionsThe method was sensitive, specific and less time-consuming and it was successfully applied in GIST patients treated with Imatinib.
      PubDate: 2017-06-16T06:30:19.102535-05:
      DOI: 10.1002/bmc.4022
  • Comparative pharmacokinetics of acteoside from total glycoside extracted
           from leaves of Rehmannia and Dihuangye total glycoside capsule in normal
           and diabetic nephropathy rats
    • Authors: Xin-Xin Dai; Shu-Lan Su, Hong-Die Cai, Dan-Dan Wei, Tian-Yao Zheng, Zhen-Hua Zhu, Hui Yan, Er-Xin Shang, Sheng Guo, Da-Wei Qian, Jin-Ao Duan
      Abstract: Rehmannia glutinosa Libosch (RG), is officially listed in the Chinese Pharmacopoeia and is widely used in China. In this paper, a sensitive and rapid ultra-performance liquid chromatography–mass spectrometry method including multiple-reaction monitoring mode was developed and applied to study the pharmacokinetic effect of acteoside from total glycoside extracted from the leaves of Rehmannia (TLR) and Dihuangye total glycoside capsule (DTG) in normal and diabetic nephropathy rats. The diabetic nephropathy rat model was induced by intraperitoneal injection of a small dose of streptozotocin and high-fat diet and plus 5% glucose drinking water. Samples of plasma of rats were obtained at different times after rats were administered TLR (7.2 g/kg) and DTG (360 mg/kg). After deproteinization by acetonitrile, the concentrations of acteoside in rats at different time points were detected by UPLC-TQ-MS method and pharmacokinetics parameters were calculated using DAS 3.2.8 software. A good linearity of acteoside was shown in the range of 8.51–3404.8 ng/m L (r2 = 0.9987). The mean extraction recovery of analyte was in the range of 63.55–79.49%, and the intra- and inter-day RSD values were
      PubDate: 2017-06-14T20:50:23.096971-05:
      DOI: 10.1002/bmc.4013
  • Severe metabolic impairment with increasing age for CYP3A and CYP2D
           substrates in rats: Possible consequences for drug development
    • Authors: Nuggehally R. Srinivas
      PubDate: 2017-06-07T20:10:21.205229-05:
      DOI: 10.1002/bmc.4009
  • Development and validation of an LC-ESI-MS/MS approach to determine a
           highly hydrophobic drug, norcantharidin palmitate, and apply to a
           preliminary pharmacokinetic study in rats
    • Authors: Xiaolin Liu; Xiaoguang Tao, Qi Zheng, Hang Xu, Yu Zhang, Tian Lei, Tian Yin, Haibing He, Xing Tang
      Abstract: In order to investigate the pharmacokinetics of norcantharidin palmitate (NCTD-PAL) in rats, we developed and validated an LC-ESI-MS/MS method. The NCTD-PAL and internal standard (triamcinoloneacetonide palmitate, TAP) were separated on a Phenomenex Kinetex®XB C18 column, and the mobile phase was composed of tetrahydrofuran (THF)–acetonitrile (20/80, v/v) and an aqueous phase containing 0.2% ammonium hydroxide at a flow rate of 0.3 mL/min. The ESI interface operated in positive mode was used to acquire the mass spectrometric data, and the transition ions were m/z 635.50  168.95 and 673.65  397.13 for NCTD-PAL and IS, respectively. The method had a linear range of 10–2000 ng/mL with a correlation coefficient of>0.99. The accuracy (RE, %) was within ±10.1%, and the intra- and inter-day precisions (RSD, %) were 10.9 and 13.8%, respectively. The extraction recovery of NCTD-PAL at different concentrations ranged from 89.3 to 102.0%. The validated approach was efficaciously applied to a pharmacokinetic study of NCTD-PAL in rats via intravenous injection. Based on these results obtained, this method is practical and suitable for a wide range of applications.
      PubDate: 2017-06-05T21:15:25.544986-05:
      DOI: 10.1002/bmc.4010
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