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  Subjects -> CHEMISTRY (Total: 846 journals)
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    - CHEMISTRY (597 journals)
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CHEMISTRY (597 journals)                  1 2 3 | Last

Showing 1 - 200 of 735 Journals sorted alphabetically
2D Materials     Hybrid Journal   (Followers: 7)
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: 31)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 17)
ACS Combinatorial Science     Full-text available via subscription   (Followers: 23)
ACS Macro Letters     Full-text available via subscription   (Followers: 22)
ACS Medicinal Chemistry Letters     Full-text available via subscription   (Followers: 39)
ACS Nano     Full-text available via subscription   (Followers: 218)
ACS Photonics     Full-text available via subscription   (Followers: 10)
ACS Synthetic Biology     Full-text available via subscription   (Followers: 20)
Acta Chemica Iasi     Open Access   (Followers: 2)
Acta Chimica Sinica     Full-text available via subscription  
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: 7)
Adsorption Science & Technology     Full-text available via subscription   (Followers: 5)
Advanced Functional Materials     Hybrid Journal   (Followers: 48)
Advanced Science Focus     Free   (Followers: 3)
Advances in Chemical Engineering and Science     Open Access   (Followers: 53)
Advances in Chemical Science     Open Access   (Followers: 12)
Advances in Chemistry     Open Access   (Followers: 12)
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: 10)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 8)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 14)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 8)
Advances in Materials Physics and Chemistry     Open Access   (Followers: 18)
Advances in Nanoparticles     Open Access   (Followers: 12)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15)
Advances in Polymer Science     Hybrid Journal   (Followers: 40)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 18)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Science and Technology     Full-text available via subscription   (Followers: 10)
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: 65)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 14)
American Journal of Chemistry     Open Access   (Followers: 25)
American Journal of Plant Physiology     Open Access   (Followers: 13)
American Mineralogist     Full-text available via subscription   (Followers: 12)
Analyst     Full-text available via subscription   (Followers: 38)
Angewandte Chemie     Hybrid Journal   (Followers: 153)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 204)
Annales UMCS, Chemia     Open Access   (Followers: 1)
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 1)
Annual Reports in Computational Chemistry     Full-text available via subscription   (Followers: 3)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 3)
Annual Reports Section B (Organic Chemistry)     Full-text available via subscription   (Followers: 7)
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: 14)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antiviral Chemistry and Chemotherapy     Hybrid Journal  
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 6)
Applied Spectroscopy     Full-text available via subscription   (Followers: 22)
Applied Surface Science     Hybrid Journal   (Followers: 26)
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: 3)
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: 9)
Biochemistry     Full-text available via subscription   (Followers: 278)
Biochemistry Insights     Open Access   (Followers: 5)
Biochemistry Research International     Open Access   (Followers: 6)
BioChip Journal     Hybrid Journal  
Bioinorganic Chemistry and Applications     Open Access   (Followers: 9)
Bioinspired Materials     Open Access   (Followers: 3)
Biointerface Research in Applied Chemistry     Open Access   (Followers: 2)
Biointerphases     Open Access   (Followers: 1)
Biology, Medicine, & Natural Product Chemistry     Open Access  
Biomacromolecules     Full-text available via subscription   (Followers: 18)
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: 4)
Bioorganic & Medicinal Chemistry     Hybrid Journal   (Followers: 109)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 99)
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: 2)
Canadian Association of Radiologists Journal     Full-text available via subscription   (Followers: 2)
Canadian Journal of Chemistry     Full-text available via subscription   (Followers: 10)
Canadian Mineralogist     Full-text available via subscription   (Followers: 3)
Carbohydrate Research     Hybrid Journal   (Followers: 26)
Carbon     Hybrid Journal   (Followers: 67)
Catalysis for Sustainable Energy     Open Access   (Followers: 6)
Catalysis Reviews: Science and Engineering     Hybrid Journal   (Followers: 8)
Catalysis Science and Technology     Free   (Followers: 6)
Catalysis Surveys from Asia     Hybrid Journal   (Followers: 3)
Catalysts     Open Access   (Followers: 7)
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: 12)
Chemical Bulletin of Kazakh National University     Open Access  
Chemical Communications     Full-text available via subscription   (Followers: 69)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 23)
Chemical Research in Chinese Universities     Hybrid Journal   (Followers: 3)
Chemical Research in Toxicology     Full-text available via subscription   (Followers: 19)
Chemical Reviews     Full-text available via subscription   (Followers: 165)
Chemical Science     Open Access   (Followers: 21)
Chemical Technology     Open Access   (Followers: 15)
Chemical Vapor Deposition     Hybrid Journal   (Followers: 4)
Chemical Week     Full-text available via subscription   (Followers: 7)
Chemie in Unserer Zeit     Hybrid Journal   (Followers: 55)
Chemie-Ingenieur-Technik (Cit)     Hybrid Journal   (Followers: 25)
ChemInform     Hybrid Journal   (Followers: 7)
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: 137)
Chemistry - An Asian Journal     Hybrid Journal   (Followers: 15)
Chemistry and Materials Research     Open Access   (Followers: 17)
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: 43)
Chemistry of Materials     Full-text available via subscription   (Followers: 189)
Chemistry of Natural Compounds     Hybrid Journal   (Followers: 9)
Chemistry-Didactics-Ecology-Metrology     Open Access  
ChemistryOpen     Open Access   (Followers: 2)
Chemkon - Chemie Konkret, Forum Fuer Unterricht Und Didaktik     Hybrid Journal  
Chemoecology     Hybrid Journal   (Followers: 2)
Chemometrics and Intelligent Laboratory Systems     Hybrid Journal   (Followers: 15)
Chemosensors     Open Access  
ChemPhysChem     Hybrid Journal   (Followers: 8)
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: 23)
Chromatography Research International     Open Access   (Followers: 7)
Clay Minerals     Full-text available via subscription   (Followers: 9)
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: 8)
Combinatorial Chemistry & High Throughput Screening     Hybrid Journal   (Followers: 3)
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: 2)
Copernican Letters     Open Access  
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 5)
Crystal Structure Theory and Applications     Open Access   (Followers: 3)
CrystEngComm     Full-text available via subscription   (Followers: 10)
Current Catalysis     Hybrid Journal   (Followers: 2)
Current Metabolomics     Hybrid Journal   (Followers: 4)
Current Opinion in Colloid & Interface Science     Hybrid Journal   (Followers: 9)
Current Research in Chemistry     Open Access   (Followers: 8)
Current Science     Open Access   (Followers: 48)
Dalton Transactions     Full-text available via subscription   (Followers: 18)
Detection     Open Access   (Followers: 2)
Developments in Geochemistry     Full-text available via subscription   (Followers: 2)
Diamond and Related Materials     Hybrid Journal   (Followers: 11)
Dislocations in Solids     Full-text available via subscription  
Doklady Chemistry     Hybrid Journal  
Drying Technology: An International Journal     Hybrid Journal   (Followers: 3)
Eclética Química     Open Access   (Followers: 1)
Ecological Chemistry and Engineering S     Open Access   (Followers: 4)
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: 2)
Environmental Chemistry     Hybrid Journal   (Followers: 8)
Environmental Chemistry Letters     Hybrid Journal   (Followers: 4)
Environmental Science & Technology Letters     Full-text available via subscription   (Followers: 5)
Environmental Science : Nano     Partially Free   (Followers: 1)
Environmental Toxicology & Chemistry     Hybrid Journal   (Followers: 19)

        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  [1583 journals]
  • A review of chromatographic methods for Ketamine and its metabolites
           Norketamine and Dehydronorketamine
    • Authors: Eylem Funda GÖKTAŞ; Filiz ARIÖZ
      Abstract: Ketamine has a synthetic, sedative, non-barbiturate and fast-acting anesthetic properties and it is commonly used in both humans and veterinary surgery. There are many analytical methods available for the qualitative and quantitative determination of Ketamine and its metabolites. This review gives information for the implementation of methods to support ketamine and its metabolites studies in researchs and it could be useful in forensic sciences in addition to doping control, human and animal clinical surgery. In this review, we have focused on sample pre-treatment and chromatographic techniques used since 2000 years for the determination of ketamine and its metabolites in biological samples. Liquid and gas chromatography coupled with various detection techniques (mass spectrometry, ultraviolet or fluorescence detection) have been used in these publications. This review gives information for the implementation of methods to support ketamine and its metabolites studies in various research applications. It could be useful in forensic sciences including doping control and also in the therapeutic drug monitoring of ketamine and nor-ketamine in human and animal clinical surgery.
      PubDate: 2017-05-27T01:15:22.178997-05:
      DOI: 10.1002/bmc.4014
       
  • 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 (UPLC-TQ-MS) including multiple-reaction monitoring mode was developed and applied to study the pharmacokinetics effect of acteoside from Total glycoside Extracted from Leaves of Rehmannia (TLR) and Dihuangye total glycoside capsule (DTG) in normal and diabetic nephropathy rats. Diabetic nephropathy rats 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 time after rats were administrated with TLR (7.2 g/kg) and DTG (360 mg/kg), after the deproteinization by acetonitrile, the concentration of acteoside in rats at different time points were detected by UPLC-TQ-MS method and pharmacokinetics parameters were calculated by DAS 3.2.8 software. A good linearity of acteoside was shown in the ranges 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 less than 8.8%. Compared with the normal group, the Cmax, AUC0–t, AUC0–∞ and CL/F corresponding dose in model group rats decreased significantly. After rats were administrated with the TLR and DTG, the acteoside reached the maximum plasma concentration was about 15 min. The method is proved to be simple, rapid, and specific, and to be suitable for the determination of acteoside in plasma of diabetic nephropathy rats and the pharmacokinetics study.
      PubDate: 2017-05-23T20:00:23.101527-05:
      DOI: 10.1002/bmc.4013
       
  • 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-Ze Huang, Zhen-Zhong Wang, Wei Xiao, Chong-Zhi Wang, Chun-Su Yuan
      Abstract: Daphne genkwa Sieb.et Zucc. is a well-known medicinal plant. This study was designed to apply the ultra-high performance liquid chromatography (UPLC) system to establish a quality control method of Daphne genkwa. Data revealed that there were fifteen common peaks in ten 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 primarily. In addition, LPS-stimulated RAW264.7 murine macrophages and DPPH assay were adopted to study the anti-inflammatory and anti-oxidation effects of Daphne Genkwa. Then the fingerprint-efficacy relationship between UPLC fingerprints and pharmacodynamic data were studied with canonical correlation analysis (CCA). Analysis results indicated that the anti-inflammatory and anti-oxidation effects were discrepant among the ten Daphne genkwa samples due to their inherent differences of chemical compositions. Taken together, this research established a fingerprint-efficacy relationship model of Daphne Genkwa plants by combining the UPLC analytic technique and pharmacological researches, which provided references for the detection of the principle components of traditional Chinese medicine on bioactivity.
      PubDate: 2017-05-22T00:55:25.829983-05:
      DOI: 10.1002/bmc.4012
       
  • Hydrophilic interaction and reversed-phase ultra-performance liquid
           chromatography TOF-MS for metabolomic analysis of Veratrum nigrum-induced
           cardiotoxicity
    • 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 analysing heart tissue metabolic profiles in mouse models and applying reversed-phase liquid chromatography mass spectrometry (RPLC-MS) and hydrophilic interaction liquid chromatography mass spectrometry (HILIC-MS) that are based on ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). An animal model of acute heart injury was established in mice via intra-gastric administration of VN. Then, electrocardiogram, echocardiograph monitoring of cardiac function and pathological examination were performed on mice both in the control and VN groups, and it was successfully 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, etc., 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: 2017-05-22T00:35:23.930359-05:
      DOI: 10.1002/bmc.4011
       
  • Development and validation of an LC-ESI-MS/MS approach to determinate 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 10-2,000 ng/mL with correlation coefficient of more than 0.99. The accuracy (RE, %) was within ±10.1%, and the intra-day 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 is suitable for a wide range of applications.
      PubDate: 2017-05-12T23:49:01.781218-05:
      DOI: 10.1002/bmc.4010
       
  • Structural identification of degradants of moexipril by LC-MS/MS
    • Authors: C. Purushotham Reddy; K. Ramakrishna, K. M. V. Narayana Rao
      Abstract: A gradient LC-MS method was developed for the identification and characterization of degradants of moexipril using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Moexipril was subjected to hydrolysis (acid, base and neutral), oxidation, photolytic and thermal degradation conditions as mentioned in ICH guidelines Q1A (R2). The drug degraded under hydrolysis, oxidation and photolytic conditions, but it was stable under thermal conditions. In total, five degradants were formed and separated on an Agilent XDB C-18 column (4.6 X 150 mm, 5 µm) in a gradient elution method. Four degradants (D1, D2, D4 and D5) under acidic conditions, three degradants (D2, D3 and D4) under basic conditions and three degradants (D1, D4 and D5) under neutral and oxidative stress conditions were formed. In addition, two degradants (D4 and D5) were formed under photolytic stress conditions. To elucidate the structures of degradants, fragmentation of moexipril and its degradants was studied by using LC-MS/MS experiments and accurate mass measurements (HRMS) data. The fragment ions in the product ion tandem mass spectra of all the degradants were compared with those of moexipril and assigned the probable structures for the degradants.
      PubDate: 2017-05-10T22:15:37.872944-05:
      DOI: 10.1002/bmc.4004
       
  • Suitability of selected chromatographic columns for analysis of fatty
           acids in dialyzed patients
    • Authors: Magdalena Pazda; Piotr Stepnowski, Tomasz Sledzinski, Michal Chmielewski, Adriana Mika
      Abstract: Gas chromatography-mass spectrometry (GC-MS) is a preferred method for fatty acid (FA) analysis in biofluids from patients with metabolic diseases. Complex characteristics of FAs make their analysis particularly challenging. Selection of an appropriate chromatographic column is particularly important component of the process as it provides optimal separation and detection of possibly all FAs present in the sample. However, no accurate protocol for comparative evaluation of capillary columns for the analysis of whole serum FA profile in patients with chronic kidney disease (CKD) has been developed thus far. Therefore, in present study four columns were examined to select the one providing optimal separation and determination of FA profiles in this group of patients. Moreover, serum FA profiles obtained with the selected column in CKD patients subjected to peritoneal dialysis and healthy controls were compared. 37 Component FAME Mix and sera from CKD patients were used to optimize chromatographic conditions and to select the most appropriate column. ZB-5 column turned out to be the most appropriate for the analysis of whole FA profile in CKD patients’ sera. Then, this column was used to compare FA profiles in patients subjected to peritoneal dialysis and in healthy controls. The analysis demonstrated many abnormalities in the FA profile of CKD patients. Further studies involving larger groups of patients presenting with other stages of CKD are required to explain the impact of the disease progression on composition of serum FAs.
      PubDate: 2017-05-10T22:15:34.528359-05:
      DOI: 10.1002/bmc.4006
       
  • UHPLC-ESI-MS/MS determination and pharmacokinetics of pinoresinol
           glucoside and chlorogenic acid in rat plasma after oral administration of
           Eucommia ulmoides Oliv extract
    • Authors: Xiaojian Gong; Qingxiang Luan, Xin Zhou, Yang Zhao, Chao Zhao
      Abstract: This study aimed to develop a specific UHPLC-ESI-MS/MS method for simultaneous determination and pharmacokinetics of pinoresinol glucoside and chlorogenic acid in rat plasma after oral administration of E. ulmoides. The chromatographic separation was achieved on a Hypersil GOLD column with gradient elution by using a mixture of 0.1% formic acid aqueous solution and acetonitrile as the mobile phase at a flow rate of 200 μL/min. A tandem mass spectrometric detection was conducted using multiple-reaction monitoring (MRM) via an electrospray ionization (ESI) source in negative ionization mode. Samples were pre-treated by a single-step protein precipitation with acetonitrile, and bergenin was used as internal standard (IS). After oral administration of 3 mL/kg E. ulmoides extract in rats, the maximum plasma concentration (Cmax) of pinoresinol glucoside, chlorogenic acid were 57.44 and 61.04 ng/mL, respectively. The time to reach the maximum plasma concentration (Tmax) were 40.00 and 23.33 min for pinoresinol glucoside and chlorogenic acid, respectively. The intra-day and inter-day precision (RSD%) values for the two analytes were less than 2.46% and 5.15%, respectively, and the accuracy (RE%) values ranged from -12.76 to 0.00. This is the first study on pharmacokinetics of bioactive compounds in rat plasma after oral administration of E. ulmoides extract.
      PubDate: 2017-05-10T22:15:32.040265-05:
      DOI: 10.1002/bmc.4008
       
  • Development and validation of HPLC-MS/MS method for the determination of
           
    • Authors: Adnan A. Khady; Haithem Alrabiah, Mohamed W. Attwa, Sabray Attia, Gamal A. E. Mostafa
      Abstract: The aim of the present study was to develop a simple, sensitive, and accurate liquid chromatography-electrospray ionization tandem mass spectrometry (ESI-MS/MS) method for the determination of lixivaptan (LIX) in mouse plasma by using vildagliptin as the internal standard (IS). A precipitation procedure was used for the extraction of LIX and vildagliptin from mouse plasma. Chromatographic separation of LIX was achieved using a C18 analytical column (50 mm × 2.1 mm, 1.8 µm) at 25 °C. The mobile phase comprised of acetonitrile and ammonium formate (10 mM, pH 3.1) (40:60, v/v) pumped at a flow rate of 0.3 mL min-1. A tandem mass spectrometer with an electrospray ionization source was used to perform the assay. Quantification of LIX at m/z 290  137 and IS at 154  97 was attained through MRM. The investigated method was authenticated following the bio-analytical method of validation guidelines of FDA. The developed method showed a good linearity over the concentration range from 5 - 500 ng mL-1, and the calibration curve was linear (r = 0.9998). The mean recovery of LIX from mouse plasma was 99.2 ± 0.68 %. All validation parameters for lixivaptan were within the levels required for acceptance. The proposed method was effectively used for a pharmacokinetic study of LIX in mouse plasma.
      PubDate: 2017-05-10T22:15:26.533961-05:
      DOI: 10.1002/bmc.4007
       
  • Development and validation of a sensitive UHPLC-MS/MS method for
           quantitative analysis of farrerol in rat plasma: Application to
           pharmacokinetic and bioavailability studies
    • Authors: Li Piao; Mingcui Zang, Yue Gu, Baohua Liu
      Abstract: Farrerol is a 2,3-dihydro-flavonoid isolated from rhododendron. In this study, a sensitive and selective ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the determination of farrerol in rat plasma. Liquid-liquid extraction by ethyl ether was used for sample preparation. Chromatographic separation was achieved on an Agilent UHPLC XDB-C18 column (2.1 mm × 100 mm, 1.8 µm) with water and methanol (30:70, v/v) as the mobile phase. An electrospray source was applied and operated in negative ion mode; selection reaction monitoring was used for quantification using target fragment ions m/z 299  179 for farrerol and m/z 267  252 for internal standard. Calibration plots were linear in the range of 2.88–1440 ng/mL for farrerol in rat plasma. Intra-day and inter-day precisions were less than 11.6%, and the accuracy ranged from –13.9% to 11.9%. The UHPLC-MS/MS method was successfully applied in pharmacokinetics and bioavailability studies of farrerol in rats.
      PubDate: 2017-05-10T22:10:22.534808-05:
      DOI: 10.1002/bmc.4005
       
  • Fast and Parallel determination of PCB 77 and PCB 180 in plasma using
           Ultra Performance Liquid Chromatography (UPLC) with diode array detection
           (DAD): A Pharmacokinetic study in Swiss albino mouse
    • Authors: N. Ramanujam; M. Sivaselvakumar, S. Ramalingam
      Abstract: A simple, sensitive and reproducible ultra-performance liquid chromatography (UPLC) method has been developed and validated for simultaneous estimation of PCB 77 and PCB 180 in mouse plasma. The sample preparation was performed by simple liquid-liquid extraction technique. The analytes were chromatographed on a Waters Acquity H class UPLC system using isocratic mobile phase conditions at a flow rate of 0.3 mL/min and Acquity UPLC BEH shield RP18 column maintained at 35 °C temperature. Quantification was performed on a photodiode array detector set at 215 nm and PCB 101 was used as internal standard (IS). PCB 77, PCB 180, and IS retention times were found to be 2.6, 4.7 and 2.8 min, respectively, and the total run time was 6 min. The method was validated for specificity, selectivity, recovery, linearity, accuracy, precision, and sample stability. The calibration curve was linear over the concentration range 10 to 3000 ng/mL for PCB 77, and PCB 180. Intra- and inter-day precisions for PCBs 77 and 180 were found to be good with % CV
      PubDate: 2017-05-08T20:30:25.570772-05:
      DOI: 10.1002/bmc.4000
       
  • Development and validation of a liquid chromatography tandem mass
           spectrometry method for the measurement of urinary catecholamines in
           diagnosis of pheochromocytoma
    • Authors: Ying Shen; Liming Cheng, Qing Guan, Huijun Li, Jie Lu, Xu Wang
      Abstract: The measurement of catecholamines in human body fluids is requested frequently for the differential diagnosis and monitoring of pheochromocytoma. The methods in most clinical laboratories focus on high performance liquid chromatography coupled with electrochemical detection which suffers from high background noise, low sensitivity, and poor separation. We reported and developed a robust high-throughput liquid chromatography tandem mass spectrometry method in routine clinical laboratories for the measurement of urinary catecholamines for diagnosis of pheochromocytoma.The method was validated for consistent linearity, good recovery (88%-112%), excellent stability and low carryover. Intra-assay and inter-assay imprecision values for catecholamines were all below 3.35% and 4.83% respectively. Dilution linearity was investigated with satisfied linearly dependent coefficients (r > 0.9988). The reference intervals were obtained from 310 results derived from patients in which the diagnosis of pheochromocytoma was excluded. This method was successfully used in our lab. The clinical characteristics of patients have been explored with satisfied sensitivity and specificity. Therefore, we have developed a reliable assay for the liquid chromatography tandem mass spectrometry measurement of catecholamines in a routine clinical laboratory. The assay requires a small volume of urine, and all analytes are measured simultaneously. The assay is rapid and reliable to execute offering the potential for routine clinical laboratories.
      PubDate: 2017-05-08T09:40:25.915065-05:
      DOI: 10.1002/bmc.4003
       
  • Screening free radical scavengers in Xiexin Tang by HPLC-ABTS-DAD-Q-TOF/MS
    • Authors: Yu-Qing Wang; Shu-Jiao Li, Guo Zhuang, Rong-Hui Geng, Xu Jiang
      Abstract: Xiexin Tang (XXT) is a traditional Chinese medicine (TCM) that has been used in herbal clinics for more than 1800 years. Many studies have shown that XXT has therapeutic effects on patients with arteriosclerosis (AS) owing to its antioxidant activity. However, there is little information about the relationship between the chemical composition of XXT and its antioxidant activity. In this study, the HPLC-ABTS-DAD-Q-TOF/MS method, which can simultaneously identify individual components and rapidly screen for antioxidant compounds, was used to screen and identify antioxidant components in XXT. The fifteen compounds identified were gluco-syringic acid, adenine, gallic acid, biflorin, cularine, 6-C-arabinose-8-C-glucose-chrysin, 6-C-glucose-8-C-arabinose–chrysin, baicalin, rhein-8-O-β-D-glucopyranoside, coptisine, epiberberine, jatrorrhizine, norwogonin, 5,7,2'-trihydroxy-6- methoxyflavone, and baicalein. In addition, the data showed that the antioxidant activity of peaks 4, 6, and 11 was lower in XXT than in its constituent herbs, while the activity of peaks 1, 2, 3, 5, 7, 8, 10, 12, 13, 14, and 15 was higher in XXT. Compound 5 had the strongest antioxidant activity in XXT, while compound 1 showed the strongest antioxidant activity among its constituent herb. The differences between antioxidant activity of major components of XXT and its constituent herbs might be due to the interaction of crude drugs that changes the solubility of active components during the decoction process. The results show that the HPLC-ABTS-DAD-Q-TOF/MS method can successfully combine on-line mass spectrometry with activity detection system. It is a useful tool for the rapid detection and identification of antioxidants, and for quantitative analysis of individual antioxidants in complex mixtures such as plant extracts. Furthermore, this method does not require extensive extract purification and fraction collection.
      PubDate: 2017-05-06T02:05:33.324831-05:
      DOI: 10.1002/bmc.4002
       
  • Identification of differential metabolic characteristics between tumor and
           normal tissue from colorectal cancer patients by gas chromatography-mass
           spectrometry
    • Authors: Wu Ning; Haijing Li, Fanqiang Meng, Jianhua Cheng, Xin Song, Guochao Zhang, Wenyue Wang, Shengming Wu, Junjian Fang, Kunpeng Ma, Jie Yang, Dongpo Pei, Fangting Dong
      Abstract: Colorectal cancer (CRC) is one of the most common human malignancies and encompasses cancers of the colon and rectum. Although the gold-standard colonoscopy screening method is effective in detecting CRC, this method is invasive and can result in severe complications for patients. The purpose of this study was to determine differences in metabolites between CRC and matched adjacent non-tumor tissues from CRC patients, to identify potential biomarkers that may be informative and developed screening methods. Metabolomic analysis was performed on clinically localized CRC tissue and matched adjacent non-tumor tissue from twenty CRC patients. Unsupervised analysis, supervised analysis, univariate analysis, and pathway analysis were used to identify potential metabolic biomarkers of CRC. The level of twenty-five metabolites in CRC tissues were significantly altered compared to the matched adjacent non-tumor tissues. Four metabolites (lactic acid, alanine, phosphate, and aspartic acid) demonstrated good area under the curve (AUC) of Receiver- Operator Characteristic (ROC) with acceptable sensitivities and specificities, indicating their potential as important biomarkers for CRC. Alterations of amino acid metabolism and enhanced glycolysis may be major factors in the development and progression of colorectal cancer. Lactic acid, alanine, phosphate, and aspartic acid could be effective diagnostic indicators for CRC.
      PubDate: 2017-05-05T08:20:41.549457-05:
      DOI: 10.1002/bmc.3999
       
  • A simple LC-MS/MS method facilitated by salting-out assisted
           liquid–liquid extraction (SALLE) to simultaneously determine
           trans-resveratrol (Res), its glucuronide and sulfate conjugates in rat
           plasma and its application to pharmacokinetic assay
    • Authors: Zhixia Qiu; Jiaojiao Yu, Yu Dai, Yue Yang, Xiaoyu Lu, Jiaqiu Xu, Zhiying Qin, Fang Huang, Ning Li
      Abstract: A simple LC-MS/MS method facilitated by salting-out assisted liquid–liquid extraction (SALLE) was applied to simultaneously investigate pharmacokinetics of trans-resveratrol (Res), its major glucuronide and sulfate conjugates in rat plasma. Acetonitrile-methanol (80:20, v/v) and ammonium acetate (10 mol∙L-1) were used as extractant and salting-out reagent to locate the target analytes in the supernatant after the aqueous and organic phase stratification, then the analytes were determined via gradient elution by LC-MS/MS in negative mode in a single run. The analytical method was validated with good selectivity, acceptable accuracy (above 85%) and low variation of precision (below 15%). SALLE showed better extraction efficiency of target glucuronide and sulfate conjugates (>80%). The method was successfully applied to determine Res and its four conjugated metabolites in rat after Res administration (intragastric, 50 mg/kg; intravenous, 10 mg/kg). The systemic exposures to Res conjugates were much higher than Res (AUC0-t, i.v, 7.43 μM∙h; p.o, 8.31 μM∙h), Res-3-O-β-D-Glucuronide was the major metabolite (AUC0-t, i.v, 66.1 μM∙h; p.o, 333.4 μM∙h). The bioavailability of Res was estimated around 22.4%. The reproducible SALLE method simplified the sample preparation, drastically improved the accuracy of the concomitant assay and gave full consideration of extraction recovery to each target analyte in bio-samples.
      PubDate: 2017-05-05T07:51:07.033743-05:
      DOI: 10.1002/bmc.4001
       
  • A comparative pharmacokinetic study of three flavonoids and three
           anthraquinones in normal and gastrointestinal motility disorders rat
           plasma after the oral administration of Wei-Chang-Shu tablet using
           high-performance liquid chromatography-tandem mass spectrometry
    • Authors: Yan Ren; Weiwei Zhao, Juanjuan Zhao, Xiangming Chen, Chen Yu, Mengan Liu
      Abstract: A simple, fast and reliable high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification and pharmacokinetic study of three flavonoids (liquiritigenin, isoliquiritigenin and formononetin) and three anthraquinones (emodin, rhein and aloe-emodin), which are the bioactive ingredients of Wei-Chang-Shu tablet found in rat plasma. After extraction by liquid-liquid extraction with ethyl acetate, chromatographic separation was achieved on an Agilent ZORBAX SB-C18 column (4.6 mm × 150 mm, 5 µm) at a flow rate of 1 mL/min by gradient elution using 0.1% aqueous acetic acid and acetonitrile. The detection was performed using a triple quadrupole mass spectrometer equipped with electrospray ionization source in the negative ionization and selected reaction monitoring mode. Method validation was performed in terms of specificity, carryover, linearity (r > 0.99), intra-/inter-day precision (1.0-10.1%), accuracy (relative error,
      PubDate: 2017-05-05T04:52:47.502272-05:
      DOI: 10.1002/bmc.3997
       
  • A simple and sensitive high-performance liquid chromatography-
           electrochemical detection assay for the quantitative determination of
           monoamines and respective metabolites in six discrete brain regions of
           mice
    • Authors: Serena A. Allen; Stephanie Rednour, Samantha Shepard, Brooks Barnes Pond
      Abstract: A rapid, sensitive, and reproducible assay is described for the quantitative determination of the monoamine neurotransmitters dopamine, norepinephrine, and serotonin, their metabolites, and the internal standard 3,4- dihydroxybenzlyamine hydro-bromide (DHBA) in mouse brain homogenate using high performance liquid chromatography with electrochemical detection. The method was validated in the following brain areas: frontal cortex, striatum, nucleus accumbens, hippocampus, substantia nigra pars compacta, and ventral tegmental area. Biogenic amines and relevant metabolites were extracted from discrete brain regions using a simple protein precipitation procedure, and the chromatography was achieved using a C18 column. The method was accurate over the linear range of 0.300 – 30 ng/mL (r = 0.999) for dopamine and 0.300 – 15 ng/mL (r = 0.999) for norepinephrine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindolacetic acid, with detection limits of approximately 0.125 ng/mL (5 pg on column) for each of these analytes. Accuracy and linearity for serotonin was observed throughout the concentration range of 0.625 – 30 ng/mL (r = 0.998) with an analytical detection limit of approximately 0.300 ng/mL (12 pg on column). Relative recoveries for all analytes were approximately ≥ 90% and the analytical run time was less than 10 min. The described method utilized minimal sample preparation procedures and was optimized to provide the sensitivity limits required for simultaneous monoamine and metabolite analysis in small, discrete brain tissue samples.
      PubDate: 2017-05-05T04:17:15.425172-05:
      DOI: 10.1002/bmc.3998
       
  • Issue information
    • Abstract: No abstract is available for this article.
      PubDate: 2017-05-03T01:23:25.304369-05:
      DOI: 10.1002/bmc.3840
       
  • Analysis of toldimfos in porcine muscle and bovine milk using liquid
           chromatography–triple quadrupole mass spectrometry
    • Authors: Dan Zhang; Jin-A Park, A. M. Abd El-Aty, Seong-Kwan Kim, Sang-Hyun Cho, Weijia Zheng, Jeong-min Choi, Jae-Han Shim, Byung-Joon Chang, Jin-Suk Kim, Ho-Chul Shin
      Abstract: An analytical method was developed for the detection of toldimfos sodium residues in porcine muscle and bovine milk using liquid chromatography–triple quadrupole tandem mass spectrometry (LC-MS/MS) analysis. The drug was extracted from muscle and milk using 10 mM ammonium formate in acetonitrile and then purified using n-hexane. The drug was well separated on a Luna C18 column using a mixture of 10 mM ammonium formate in ultrapure water (A) and acetonitrile (B) as the mobile phase. Good linearity was achieved over the tested concentration range (0.005 – 0.03 mg/kg) in matrix-matched standard calibration. The determination coefficients (R2) were 0.9942 and 0.9898 for muscle and milk, respectively. Fortified porcine muscle and bovine milk contained concentrations equivalent to and twice the limit of quantification (LOQ = 0.005 mg/kg) yield recoveries in the range of 75.58 – 89.74% and relative standard deviations (RSDs) of ≤ 8.87%. Samples collected from large markets located in Seoul, Republic of Korea, tested negative for toldimfos sodium residue. In conclusion, ammonium formate in acetonitrile can effectively extract toldimfos sodium from porcine muscle and bovine milk without solid-phase extraction, which is usually required for cleanup before analysis. This method can be applied for the routine analysis of toldimfos in foods of animal origins.
      PubDate: 2017-04-27T13:24:19.308045-05:
      DOI: 10.1002/bmc.3996
       
  • An HPLC method for simultaneous quantitative determination of seven
           secoiridoid glucosides separated from the roots of Ilex pubescens
    • Authors: Yang Zhang; Huan Xiong, Jiayi Bi, Guiyun Zhao, Yi Yang, Xue Chen, Yuncong Li, Chongyu Zhang, Guogang Zhang
      Abstract: A simple and specific high-performance liquid chromatographic method has been developed and validated to simultaneously determine seven secoiridoid glucosides for the first time. And three of them were separated from the ethanolic extract of the roots of Ilex pubescens for the first time, namely nuezhenide A, ligusides B and oleonuezhenide. In quantitative analysis, all of the calibration curves showed good linear regression (r > 0.999) within the tested ranges, and the mean recoveries of three different concentrations ranged from 97.6 ~ 101.2%. The limit of detection and limit of quantification were lower than 4.18 and 11.63 ng/mL, respectively. The relative standard deviation for repeatability and the precision of seven analytes were less than 3.4% and 1.9%. The established method was successfully applied to simultaneous determination of seven secoiridoid glucosides in 11 batches of samples collected from different habitats in China.
      PubDate: 2017-04-25T10:30:35.098692-05:
      DOI: 10.1002/bmc.3995
       
  • A novel mass spectrometry–based method for simultaneous determination of
           asymmetric and symmetric dimethylarginine, L-arginine, and L-citrulline
           optimized for LC-MS-TOF and LC-MS/MS
    • Authors: Jerzy Wiśniewski; Mariusz G. Fleszar, Joanna Piechowicz, Małgorzata Krzystek-Korpacka, Angelika Chachaj, Andrzej Szuba, Katarzyna Lorenc-Kukula, Leszek Masłowski, Wojciech Witkiewicz, Andrzej Gamian
      Abstract: Nitric oxide (NO) is a regulatory molecule involved in many biological processes. NO is produced by nitric oxide synthase by conversion of L-arginine to L-citrulline. L-arginine methylated derivatives, asymmetric and symmetric dimethylarginines (ADMA and SDMA), regulate L-arginine availability and the activity of nitric oxide synthase. As such, they have been frequently investigated as potential biomarkers in pathologies associated with dysfunctions in NO synthesis. Here, we present a new multistep analytical methodology based on liquid chromatography combined with mass spectrometry for the accurate identification of L-arginine, L-citrulline, ADMA, and SDMA. Compounds are measured as stable 2,3,4,5,6-pentafluorobenzoyl chloride derivatives, which allows for simultaneous analysis of all compounds through chromatographic separation of ADMA and SDMA using a reverse phase column. Serum aliquots (100 μL) were spiked with isotope-labeled internal standards and sodium carbonate buffer. The derivatization process was carried out at 25 °C for 10 minutes using pentafluorobenzoyl chloride as derivatization reagent. Calibration demonstrated good linearity (R2 = 0.9966-0.9986) for all derivatized compounds. Good accuracy (94.67–99.91%) and precision (1.92–11.8%) were observed for the quality control samples. The applicability of the method was evaluated in a cohort of angiological patients and healthy volunteers. The method discerned significantly lower L-arginine, L-citrulline in angiologic patients. This robust and fast LC-ESI-MS method may be a useful tool in quantitative analysis of L-arginine, ADMA, SDMA and L-citrulline.
      PubDate: 2017-04-24T00:45:34.810786-05:
      DOI: 10.1002/bmc.3994
       
  • Therapeutic drug monitoring of Mitotane: analytical assay and patient
           follow-up
    • Authors: Catherine Feliu; Yoann Cazaubon, Helene Guillemin, Damien Vautier, Olivier Oget, Hervé Millart, Claire Gozalo, Zoubir Djerada
      Abstract: BackgroundAdrenocortical carcinoma (ACC) is an aggressive malignancy of the adrenal gland. Mitotane (o,p′-DDD) is the most effective chemotherapy for ACC. According to literature, mitotane plasma trough concentrations within 14-20 mg.L1 are correlated with a higher response rate with acceptable toxicity. Therapeutic drug monitoring (TDM) of mitotane is therefore recommended. The aim of this study was to propose a robust, and simple method for mitotane quantification in plasma. The validation procedures were based on international guidelines.MethodsSample preparation consisted in a single protein precipitation with methanol using 100 μL of plasma. The supernatant was submitted to liquid chromatography coupled with ultra-violet detection at 230 nm.ResultsMitotane retention time was 7.1 minutes. Limit of detection was 0.1 mg.L-1 and limit of quantification was 0.78 mg.L-1. The assay demonstrated a linear range of 0.78 to 25 mg.L-1 with correlation coefficients (r2) at 0.999. Inter- and intra-assay precision were less than 4.85 %. Evaluation of accuracy showed a deviation less than 13.69 % from target concentration at each quality control level.ConclusionThis method proved easy and rapid to perform mitotane TDM and required a small volume of sample. It was successfully applied to routine TDM in our laboratory.
      PubDate: 2017-04-22T08:26:31.738109-05:
      DOI: 10.1002/bmc.3993
       
  • UHPLC-Q-TOF-MS/MS based screening and characterization of metabolites of
           cnidilin in human liver microsomes
    • Authors: Lin Yuan; Yuqian Zhang, Man Liao, Yanyan Liu, Changchen Wan, Lantong Zhang
      Abstract: Cnidilin is an active natural furocoumarin ingredient originating from well-known traditional Chinese medicine Radix Angelicae dahuricae. In the present study, an efficient approach was developed for the screening and identification of cnidilin metabolites using ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. In this approach, an on-line data acquisition method multiple mass defect filter (MMDF) combined with dynamic background subtraction was developed to trace all probable metabolites. Based on this analytical strategy, a total of 24 metabolites of cnidilin were detected in human liver microsomal incubation samples and the metabolic pathways were proposed. The results indicated that oxidation was the main biotransformation route for cnidilin in human liver microsomes (HLM). In addition, the specific cytochrome P450 (CYP) enzymes involved in the metabolism of cnidilin were identified using chemical inhibition and CYP recombinant enzymes. The results showed that CYP1A2 and CYP3A4 might be the major enzymes involved in the metabolism of cnidilin in HLM. The relationship between cnidilin and the CYP450 enzymes could provide us a theoretical basis of the pharmacological mechanism.
      PubDate: 2017-04-21T17:06:19.950012-05:
      DOI: 10.1002/bmc.3992
       
  • Carboxymethyl β-cyclodextrin as chiral selector in capillary
           electrophoresis: enantioseparation of 16 basic chiral drugs and its chiral
           recognition mechanism associated with drugs’ structural features
    • Authors: Linlin Fang; Yueying Du, Xiaoyu Hu, Linda Luo, Xin Guo, Xingjie Guo, Jia Yu
      Abstract: Herein we present the enantioseparation of 10 cardiovascular agents and 6 bronchiectasis drugs including propranolol, carteolol, metoprolol, atenolol, pindolol, esmolol, bisoprolol, bevantolol, arotinolol, sotalol, clenbuterol, procaterol, bambuterol, tranterol, salbutamol and terbutaline sulfate using carboxymethyl-β-cyclodextrin (CM-β-CD) as chiral selector. To our knowledge, there is no literature about using CM-β-CD for separating carteolol, esmolol, bisoprolol, bevantolol, arotinolol, procaterol, bambuterol and tranterol. During the course of work, changes in pH, CM-β-CD concentration, buffer type and concentration were studied in relation to chiral resolution. Excellent enantiomeric separations were obtained for all 16 compounds, especially for procaterol, impressive resolution value, up to 17.10 was obtained. Particularly, most of them were achieved rapid separations within 20 minutes. Given the fact that enantioseparation results rely on analytes’ structural characters, the possible separation mechanisms were discussed. Besides, in order to obtain faster separation for propranolol enantiomers in practical application, the effective length of capillary was innovatively shortened from 45 cm to 30 cm. After the validation, the method was successfully applied to the enantiomeric purity determination of propranolol in the formulation of drug substances.
      PubDate: 2017-04-21T17:01:40.831238-05:
      DOI: 10.1002/bmc.3991
       
  • Simultaneous quantification and semi-quantification of Amentoflavone and
           its metabolites in human intestinal bacteria by liquid chromatography
           Orbitrap high resolution mass spectrometry
    • Authors: Yiyun Qian; Shu Jiang, Zhenhua Zhu, Qi Wang, Shulan Su, Jinhua Tao, Jin-ao Duan
      Abstract: A quick, easy, effective method followed by ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap MS) was developed for the simultaneous identification and quantification of the metabolites produced by Amentoflavone (AMF) in human intestinal bacteria from human feces. The method validated for quantification of AMF concerning precision, accuracy, recovery, matrix effect, stability and limits showed acceptable results. Compared the blank human intestinal bacteria chromatography, three metabolites were presumed based on high-accuracy protonated precursors and multi-stage mass spectrometry (MSn) using the proposed strategy. At the same time, a new method was developed for semi-quantification of three metabolites. In 24 h, we described the trend of concentration-time curves of the AMF and its metabolites. Moreover, the main metabolic pathway of the AMF was clarified in human intestinal bacteria. The method was validated and successfully applied to detection and quantification of AMF and its metabolites.
      PubDate: 2017-04-20T16:07:21.336991-05:
      DOI: 10.1002/bmc.3990
       
  • Validated UHPLC-MS/MS assay for quantitative determination of etoposide,
           gemcitabine, vinorelbine and their metabolites in lung cancer patients
    • Authors: Xiaobin Gong; Le Yang, Feng Zhang, Youtian Liang, Shouhong Gao, Ke Liu, Wansheng Chen
      Abstract: A fully valid ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC- MS/MS) method was developed for the determination of etoposide, gemcitabine, vinorelbine and their metabolites (etoposide catechol, 2’,2’-difluorodeoxyuridine and 4-O-deacetylvinorelbine) in human plasma. Multiple reaction monitoring (MRM) mode was performed with an electrospray ionization (ESI) interface operating in both the positive and negative ion modes per compound. The method required only 100 μL plasma with a one-step simple de-proteinization procedure, and a short run time of 7.5 min per sample. A Waters ACQUITY UPLC HSS T3 column (2.1 × 100 mm, 1.8 µm) provided chromatographic separation of analytes using a binary mobile phase gradient (A, 0.1% formic acid in acetonitrile, v/v; B, 0.1% formic acid in water, v/v). Linear coefficients of correlation were >0.995 for all analytes. The relative deviation of this method was
      PubDate: 2017-04-13T17:15:43.207767-05:
      DOI: 10.1002/bmc.3989
       
  • Retention of glycopeptides analyzed using hydrophilic interaction
           chromatography is influenced by charge and carbon chain length of
           ion-pairing reagent for mobile phase
    • Authors: Kenichiro Furuki; Toshimasa Toyo'oka
      Abstract: Characterization of the glycans of glycoproteins is essential for the development and production of biologics. Numerous methods are available for analyzing the glycans of glycoproteins directly and labeled glycans. Nevertheless, glycopeptides are difficult to resolve because of their exceptional complexity and the microheterogeneity of glycans. These properties represent technical challenges to efforts to insure the accurate characterization of biopharmaceuticals to comply with regulatory requirements. Therefore, we investigated the retention behavior of peptides and glycopeptides in hydrophilic interaction chromatography (HILIC)-mode HPLC in the presence of ion-pairing reagents. Anionic ion-pairing reagents decreased the retention times of glycopeptides and improved resolution in the presence of higher concentrations or hydrophobicities of ion-pairing reagent. Anionic ion-pairing reagents increased retention times of larger glycans because of their increased hydrophilicity. In contrast, in the presence of cationic ion-pairing reagents, the retention times of glycopeptides with greater numbers of sialic acid residues decreased. It is appropriate to add an anionic ion-pairing reagent to the mobile phase for good separation of glycopeptides. The collision cross-sectional area values of glycopeptides determined using electrospray ionization-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS) correlated with retention times. These findings support the implementation of HILIC-mode HPLC to improve the characterization of glycosylated biopharmaceuticals.
      PubDate: 2017-04-13T16:50:29.01561-05:0
      DOI: 10.1002/bmc.3988
       
  • Simultaneous determination of difenoconazole, trifloxystrobin and its
           metabolite trifloxystrobin acid residues in watermelon under field
           conditions by GC − MS/MS
    • Authors: Di Kang; Haizhen Zhang, Yuling Chen, Fei Wang, Lihong Shi, Deyu Hu, Kankan Zhang
      Abstract: An optimized QuEChERS method for the simultaneous determination of difenoconazole, trifloxystrobin and its metabolite trifloxystrobin acid residues in watermelon and soil was developed and validated by gas chromatography with tandem mass spectrometry. The samples were extracted with acetonitrile (1% formic acid) and cleaned up by dispersive solid-phase extraction with octadecylsilane sorbent. The limit of quantification of the method was 0.01 mg/kg, and the limit of detection was 0.003 mg/kg for all three analytes. The recoveries of the fungicides in watermelon, pulp and soil were 72.32 − 99.20% for difenoconazole, 74.68 − 87.72% for trifloxystrobin and 78.59 − 92.66% for trifloxystrobin acid with relative standard deviations of 1.34 − 14.04%. The dissipation dynamics of difenoconazole and trifloxystrobin in watermelon and soil followed the first-order kinetics with half-lives of 3.2 − 8.8 days in both locations. The final residue levels of difenoconazole and trifloxystrobin were below 0.1 mg/kg (maximum residue level (MRL) set by China) and 0.2 mg/kg (MRL set by European Union), respectively, in pulp samples collected 14 days after the last application. These results could help Chinese authorities to establish MRL of trifloxystrobin in watermelon and provide guidance for the safe and proper application of both fungicides on watermelon.
      PubDate: 2017-04-12T05:18:22.227777-05:
      DOI: 10.1002/bmc.3987
       
  • Analytical challenges in quantifying abiraterone with LC-MS/MS in human
           plasma
    • Authors: Guillemette E. Benoist; Eric Meulen, Floor J. E. Lubberman, Winald R. Gerritsen, Tineke J. Smilde, Jack A. Schalken, Jan H. Beumer, David M. Burger, Nielka P. Erp
      Abstract: A method was developed and validated to quantify abiraterone in human plasma. During assay development several analytical challenges were encountered: limited stability in patient samples, adsorption to glass, co-elution with metabolites, and carry-over issues. Limited stability (2 h) was found for abiraterone in fresh plasma as well as whole blood at ambient temperature. When kept at 2-8 °C, abiraterone in plasma was stable for 24 h and in whole blood for 8 h.Adsorption of abiraterone to glass materials was addressed by using polypropylene throughout the method. Carry-over was reduced to acceptable limits by incorporating a third mobile phase into the gradient. The chromatographic separation of abiraterone with its multiple metabolites was addressed by using a longer analytical column and adjusting the gradient. Abiraterone was extracted by protein precipitation, separated on a C18-column with gradient elution and analyzed with tandem quadrupole mass spectrometry in positive ion mode. A stable deuterated isotope was used as the internal standard. The assay ranges from 1-500 ng/mL. Within–and between day precisions and accuracies were below 13.4% and within 95-102%. This bioanalytical-method was successfully validated and applied to determine plasma concentrations of abiraterone in clinical studies and in regular patient care for patients with metastatic castration resistant prostate cancer.
      PubDate: 2017-04-03T03:30:21.080145-05:
      DOI: 10.1002/bmc.3986
       
  • RP HPLC enantioseparation of β-adrenolytics using micellar mobile
           phasewithout organic solvents
    • Authors: Shiv Alwera; Ravi Bhushan
      Abstract: Enantioseparation of a few commonly administered racemic β-adrenolytics (namely, carvedilol, betaxolol, salbutamol, and bisoprolol) has been achieved using a water micellar mobile phase containing surfactants (SDS and Brij-35) without organic solvents as a new approach in RPHPLC. Two CDRs based on enantiomerically pure (S)-(−)-levofloxacin were synthesized using N-hydroxysuccinimide and N-hydroxybenzotriazole as the activation auxiliaries. Diastereomeric derivatives of the chosen β-adrenolytics were synthesized under microwave irradiation in a very short reaction time. The (S)-(−)-levofloxacin moiety enhanced molar absorbance of the diastereomeric derivatives resulting into very low LOD (1.618 ng mL−1 and 4.902 ng mL−1, respectively, for diastereomeric derivatives of (RS)-Bxl and better resolution with lower retention times (for all the analytes), in comparison to literature reports. There was 15-20 times less consumption of mobile phase because of lower retention time.
      PubDate: 2017-03-31T04:10:44.495172-05:
      DOI: 10.1002/bmc.3983
       
  • Contents Variation Analysis of Free Amino Acids, Nucleosides and
           Nucleobases in Semen sojae praeparatum Fermentation Using UFLC-QTRAP MS
    • Authors: Chuan Chai; Xiaobing Cui, Chenxiao Shan, Sheng Yu, Hongmei Wen
      Abstract: UFLC–QTRAP MS was used to develop a sensitive and rapid method of evaluating content variation during Semen sojae praeparatum (SSP) fermentation. It did this through the simultaneous quantification of 22 free amino acids (FAAs) and 16 nucleosides and nucleobases (Ns) in the raw materials and processed products of SSP. The method was shown to be reproducible and accurate. The limits of detection (LOD) and quantity (LOQ) values were between 0.09-168.75 and 0.31-562.50 ng/mL for the 38 analytes, respectively. The data was examined through Principal Component Analysis (PCA) to compare the content variations. The quantitative results showed that the ingredients were properly determined in most of the samples and were converted regularly throughout the SSP fermentation process. These results correspond to the morphologic changes and PCA results.
      PubDate: 2017-03-31T04:10:31.342971-05:
      DOI: 10.1002/bmc.3985
       
  • Sensitive and Specific LC-ESI-MS/MS Method for Determination of ZYDPLA1, a
           Novel long acting DPP4 Inhibitor in Rat Plasma: An application for
           Toxicokinetics Study in Rats
    • Authors: Poonam Giri; Nirmal Patel, Bharat Patel, Harilal Patel, Rajesh Bahekar, Nuggehally R. Srinivas, Pankaj R. Patel, Ranjit Desai
      Abstract: A rapid and highly specific assay was developed and validated for estimation ofZYDPLA1 in rat plasma using liquid chromatography coupled to tandem mass spectrometry with positive electrospray ionization. Method validation comprised of parameters such as: specificity, matrix effect, precision, accuracy, recovery, stability etc. The assay procedure involved a simple protein precipitation of ZYDPLA1 and alprazolam (internal standard, IS) from rat plasma using acetonitrile. Chromatographic separation was achieved with a gradient mobile phase comprising of (A) 0.2% ammonia in purified water, (B) 0.1% formic acid in IPA: methanol (1:1 v/v) and (C) acetonitrile at a flow rate of 1 mL/min on an ACE-5, C18 (4.6 x 50 mm) column with run time of 5.5 min. The quantitation of ZYDPLA1 was achieved by summation of four MRM transitions (m/z 399.7  383.0, 399.7  276.10, 399.7  153.20, and 399.7  127.20), while that of IS was by a single MRM transition (m/z 309.10  281.00). The lower limit of quantitation achieved was 0.01μg/mL and the method showed linearity from 0.01 to 25 µg/mL. The intra- and inter-day precision (% CV) of the quality control sampleswas within8.81%and accuracy was ±10% of nominal values.This novel method wasapplied for evaluation of Toxicokinetics of ZYDLA1 in rats.
      PubDate: 2017-03-31T04:10:24.705228-05:
      DOI: 10.1002/bmc.3984
       
  • Determination of (4-(1,3-dioxo-1,3-dihydro-2H-isoindol-
           2-yl)-N′-[(4-ethoxyphenyl) methylidene] benzohydrazide, a novel
           anti-inflammatory agent, in biological fluids by UPLC-MS/MS: Assay
           development, validation and in vitro metabolic stability study
    • Authors: Muzaffar Iqbal; Mashooq A. Bhat, Mohammad Raish, Essam Ezzeldin
      Abstract: A thalidomide analogue, (4-(1,3-dioxo-1,3-dihydro-2H-isoindol- 2-yl)-N′-[(4-ethoxyphenyl) methylidene] benzohydrazide), has been identified as a promising broad spectrum anti-inflammatory agent in previous study. In this study, a sensitive and selective UPLC-MS/MS assay was developed and validated for its determination in rat plasma samples. The chromatographic separation was performed on Aquity BEH C18 column using mobile phase comprising of acetonitrile and 10 mM ammonium acetate in the ratio of 85:15, at flow rate of 0.3 mL min-1. The detection and quantification were performed in positive multiple reaction monitoring mode by parent to daughter ion transition of 414.06 ˃ 148.05 for analyte and 411.18 ˃ 191.07 for internal standard (risperidone), respectively using electrospray ionization source. The sample extraction process consisted of liquid liquid extraction method using diethyl ether as extracting solvent. The assay was validated by following FDA guideline and all parameters were found to be within the acceptable limits. The linearity was between 10.1 - 2500 ng mL-1 and LLOQ was 10.1 ng mL-1. The reported results indicate that the assay could meet the requirement for analysis of this compound in trace amounts expected to the present in actual samples. Further, in vitro metabolic stability study was performed in rat liver microsomes by using the validated assay.
      PubDate: 2017-03-31T03:49:02.28342-05:0
      DOI: 10.1002/bmc.3981
       
  • LC/Q-TOF profile and preliminary stability studies of an enriched
           flavonoid fraction of Cecropia pachystachya Trécul leaves with potential
           antidepressant-like activity
    • Authors: Caroline F. Ortmann; Helena M. Abelaira, Gislaine Z. Réus, Zuleide M. Ignácio, Vitor Clasen Chaves, Talitha Caldas dos. Santos, Pâmela Carvalho, Anelise S. Carlessi, Livia Bruchchen, Lucineia G. Danielski, Simone Gonçalves Cardoso, Angela M. Campos, Fabricia Petronilho, Joyce Rebelo, Meline O. S. Morais, Francieli Vuolo, Felipe Dal-Pizzol, Emilio L. Streck, João Quevedo, Flávio H. Reginatto
      Abstract: There is an increasing interest in natural antioxidants that are candidates for prevention of brain damage occurring in major depressive disorders. Cecropia pachystachya is a tropical tree species of Central and South America and is a rich source of polyphenols, especially flavonoids. The aim of this study was to characterize the flavonoid profile of an enriched flavonoid fraction of C. pachystachya (EFF-Cp) and evaluate the antidepressant-like effects of its acute administration in behavior, cytokine levels, oxidative stress and energy metabolism parameters. The EFF-Cp chemical characterization was performed by HPLC/DAD and LC/QTOF. The antidepressant-like effects were performed by forced swimming test (FST), splash test and open field test. EFF-Cp showed 15 flavonoids, including 7 new glycosyl flavonoids for C. pachystachya. Quantitatively EFF-Cp showed isoorientin (43.46 mg/g), orientin (23.42 mg/g) and isovitexin (17.45 mg/g) as major C-glycosylflavonoids. Also, EFF-Cp at the dose of 50 mg/kg and 100 mg/kg reduced the immobility time in FST, without changing the locomotor activity and grooming time. In addition, EFF- Cp was able to prevent the oxidative damage in some brain areas. In conclusion, the results of this study suggest that enriched C-glycosyl flavonoid fraction of Cecropia pachystachya (EFF- Cp) exerts antidepressant-like effects by its antioxidant properties.
      PubDate: 2017-03-31T02:40:57.57073-05:0
      DOI: 10.1002/bmc.3982
       
  • A chiral LC-MS/MS method for the enantioselective determination of R-(+)-
           and S-(-)-pantoprazole in human plasma and its application to a
           pharmacokinetic study of S-(-)-pantoprazole sodium injection
    • Authors: Huiwen Jiao; Yueqi Li, Luning Sun, Hongwen Zhang, Liyuan Yu, Lei Yu, Ziqingyun Yuan, Lijun Xie, Juan Chen, Yongqing Wang
      Abstract: Pantoprazole, a proton pump inhibitor, is clinically used for the treatment of peptic diseases. An enantioselective LC-MS/MS method was developed and validated for the simultaneous determination of pantoprazole enantiomers in human plasma. Pantoprazole enantiomers and the internal standard (IS) were extracted from plasma using acetonitrile. Chiral separation was carried on a Chiralpak IE column using the mobile phase consisted of 10 mM ammonium acetate solution containing 0.1% acetic acid-acetonitrile (28:72, v/v). The mass spectrometric analysis was performed on an API 4000 mass spectrometer. The multiple reactions monitoring (MRM) transitions of m/z 384.1  200.1 and 390.1  206.0 were used to quantify pantoprazole enantiomers and IS, respectively. For each enantiomer, no apparent matrix effect was found, the calibration curve was linear over 5.00-10000 ng/mL, the intra- and inter-day precisions were below 10.0%, and the accuracy was within the range of -5.6% to 0.6%. This method was applied to the stereoselective pharmacokinetic studies in human after intravenous administration of S-(-)-pantoprazole sodium injections. No chiral inversion was observed during sample storage, preparation procedure and analysis. While R-(+)-pantoprazole was detected in human plasma with a slightly high concentration, which implied that S-(-)-pantoprazole may convert to R-(+)-pantoprazole in some subjects.
      PubDate: 2017-03-29T05:40:21.596166-05:
      DOI: 10.1002/bmc.3980
       
  • Use of LC-QqQ-MS for the detection of emodin metabolites in rat bile and
           urine
    • Authors: Songyan Wu; Yaqing Zhang, Zunjian Zhang, Rui Song
      Abstract: Emodin is the representative form of rhubarb, which is widely used in traditional Chinese medicine for the treatment of purgative, anti-inflammatory, antioxidative and antiviral, etc. Previous reports demonstrated that emodin glucuronide was the major metabolite in plasma. Due to the extensive conjugation reactions of polyphenols, the aim of this study was to identify the metabolites of emodin in rat bile and urine. Neutral loss and precursor ion scan methods of triple-quadrupole mass spectrometer revealed 13 conjugated metabolites in rat bile and 22 metabolites in rat urine, which including 4 phase I and 18 phase II metabolites. The major metabolites in rat bio-samples were emodin glucuronoconjugates. Moreover, rhein monoglucuronide, chrysophanol monoglucuronide and rhein sulfate were proposed for the first time after oral administration of emodin. Overall, liquid chromatography hybrid triple-quadrupole mass spectrometry (LC-QqQ-MS) analysis leads to the discovery of several novel emodin metabolites in rat bile and urine and underscores that conjugated with glucuronic acid is the main metabolic pathway.
      PubDate: 2017-03-25T08:30:38.348972-05:
      DOI: 10.1002/bmc.3979
       
  • Screening and identification of multiple constituents and their
           metabolites of Zhi-zi-chi decoction in rat urine and bile by
           UPLC-Q-TOF-MS/MS
    • Authors: Wei Feng; Qiuju Dong, Minyan Liu, Si Li, Ting Liu, Xinguo Wang, Liying Niu
      Abstract: Zhi-zi-chi decoction (ZZCD) is a classical formula widely used in Chinese clinical application. In the present study, a novel and efficient strategy has been developed for screening and identification of multiple constituents and their metabolites of ZZCD using ultra high performance liquid chromatography combined with triple TOF mass spectrometry. The novel approach of an on-line data acquisition method dependent on multiple mass defect filter and dynamic background subtraction is combined with multiple data processing techniques. Firstly, a total of 109 potential bioactive compounds were detected in ZZCD. Based on the same instrumental conditions, 100 compounds were found in rat biofluids after oral administration of ZZCD, including 61 original compounds of ZZCD as well as 39 metabolites. Conjugations with sulfate, glucuronate, and amino acids were found as the predominant metabolic reaction of ZZCD. As more xenobiotics were detected in urine than those in bile, it demonstrated that multiple components of ZZCD have undergone comprehensive renal excretion. This study reported the urinary and biliary excretion in rats after oral administration of ZZCD for the first time. The present study expands our knowledge about the constituents and metabolism of ZZCD, which could be very useful for further pharmacological and clinical studies of ZZCD.
      PubDate: 2017-03-23T00:50:26.271968-05:
      DOI: 10.1002/bmc.3978
       
  • Comparative Pharmacokinetic study of Pyranocoumarins and Khellactone in
           normal and acute lung injury rats after oral administration of Peucedanum
           Praeruptorum Dunn extracts using a rapid and sensitive LC-MS/MS method
    • Authors: An Kang; Tong Xie, Dong Zhu, Yu Dong, Hongmei Wen, Yuqiong Pei, Jinjun Shan, Liuqing Di
      Abstract: Pyranocoumarins are the main constitutes in Peucedanum praeruptorum Dunn, and possess various biological activities. In this article, we developed and validated a rapid and sensitive liquid chromatography (LC) tandem mass spectrometry method for targeted quantification of praeruptorin A, praeruptorin B, praeruptorin E and khellactone, a common metabolite of these pyranocoumarins in rat plasma samples. We then performed a comparative pharmacokinetic study of these pyranocoumarins and khellactone in normal and LPS induced acute lung injury (ALI) rats following oral administration of Peucedanum praeruptorum Dunn extracts. Calibration curves gave desirable linearity (r > 0.99) and the LLOQs were sufficient for quantitative analysis. The precision and accuracy were assessed by intra-batch and inter-batch assays, and the relative standard deviation (RSD) were all within 10.23% and the accuracy (RE) was between -5.52% and 8.68%. The extraction recoveries, matrix effects and stability were also acceptable. The pharmacokinetic study revealed that the AUC0-t of khellactone in ALI rats was significantly decreased compared with the normal rats. Meanwhile, the systemic exposures of these pyranocoumarins were slightly higher in the ALI rats than those in normal rats. The pharmacokinetic study in pathological state might provide more comprehensive information to guide the clinical usage of Peucedanum Praeruptorum Dunn.
      PubDate: 2017-03-21T03:16:21.890435-05:
      DOI: 10.1002/bmc.3977
       
  • Free mycophenolic acid determination in human plasma ultrafiltrate by a
           validated liquid chromatography-tandem mass spectrometry method.
    • Authors: Paulina Łuszczyńska; Tomasz Pawiński, Paweł K. Kunicki, Katarzyna Sikorska, Ryszard Marszałek
      Abstract: ObjectivesThe aim of this study was to develop and fully validate LC-MS/MS method for free mycophenolic acid (MPA) concentration measurements in plasma ultrafiltrate that will be reliable and simple in preparation with deuterated MPA (MPA-d3) chosen as an internal standard.MethodsThe chromatographic separation was made with Zorbax Eclipse XDB-C18 column (4.6x150 mm) using a gradient of two solutions as a mobile phase: A) water and B) methanol, each containing 0.1% formic acid and 2.5 mM ammonium acetate.ResultsSatisfactory repeatability of retention times was achieved with average values of 7.54 ± 0.20 min and 7.50 ± 0.19 min for MPA and MPA-d3, respectively. The method was selective, with no carry-over or matrix effect observed. The analytical range was proven for MPA ultrafiltrate concentrations of 1-500 ng/mL. The accuracy and precision fell within the acceptance criteria for intraday (accuracy: 100.63-110.46%, imprecision: 6.23-7.76%), as well as interday assay (accuracy: 98.81-110.63%, imprecision: 5.36-10.22%). The method was used for free MPA determination in plasma samples from patients treated with mycophenolate mofetil.ConclusionsTo our best knowledge this is the first LC-MS/MS method for free MPA monitoring using MPA-d3 that allows to measure plasma ultrafiltrate concentrations as low as 1 ng/mL.
      PubDate: 2017-03-20T01:45:32.70541-05:0
      DOI: 10.1002/bmc.3976
       
  • UHPLC-MS/MS method for the determination of omarigliptin in rat plasma and
           its application to a pharmacokinetic study in rats
    • Authors: Meng-fang Li; Xiao-xia Hu, Ai-qun Ma
      Abstract: Omarigliptin is a novel long-acting DPP-4 inhibitor used for the treatment of T2DM. In this work, a sensitive and selective UHPLC-MS/MS method was developed and validated for determination of omarigliptin in rat plasma. Sample preparation was performed by protein precipitation with acetonitrile. Chromatographic separation of analytes was achieved on a RRHD Eclipse Plus C18 column (2.1 × 50 mm, 1.8 µ), using gradient mobile phase (0.1% formic acid-acetonitrile) at a flow rate of 0.4 mL/min. Detection was performed in multiple reaction monitoring mode, with target fragment ions m/z 399.1  152.9 for omarigliptin and m/z 237.1  194 for IS. The total run time was 4 min. Retention time of omarigliptin and IS was 1.25 and 2.12 min, respectively. RSD% of the intra- and inter-day precision was below 10.0%, and accuracy was between 97.9% and 105.3%. Calibration curve was established over the range of 2-5000 ng/mL with good linearity. The LLOQ and LOD of omarigliptin were 2 ng/mL and 0.25 ng/mL, respectively. Mean recoveries were in the range of 87.3-95.1% for omarigliptin. No matrix effect was observed in this method. This novel method has been successfully applied to a pharmacokinetic study of omarigliptin in rats. The absolute bioavailability of omarigliptin was identified as high as 87.31%.
      PubDate: 2017-03-19T21:30:33.498865-05:
      DOI: 10.1002/bmc.3975
       
  • Effect of alprazolam on rat serum metabolic profiles
    • Authors: Yan Li; Gaotong Lin, Bingbao Chen, Jing Zhang, Lingtian Wang, Zixia Li, Yungang Cao, Congcong Wen, Xuezhi Yang, Gaozhong Cao, Xianqin Wang, Guoquan Cao
      Abstract: We developed a serum metabolomic method by gas chromatography–mass spectrometry (GC–MS) to evaluate the effect of alprazolam in rats. The GC–MS with HP-5MS (0.25 μm × 30 m × 0.25 mm) mass was conducted in electron impact ionization (EI) mode with electron energy of 70 eV, and full-scan mode with m/z 50–550. The rats were randomly divided to four groups, three alprazolam-treated groups and a control group. The alprazolam-treated rats were given 5, 10 or 20 mg/kg (low, medium, high) of alprazolam by intragastric administration each day for 14 days. The serum samples were corrected on the seventh and fourteenth days for metabolomic study. The blood was collected for biochemical tests. Then liver and brain were rapidly isolated and immersed for pathological study. Compared with the control group, on the seventh and fourteen days, the levels of d-glucose, 9,12-octadecadienoic acid, butanoic acid, l-proline, d-mannose and malic acid had changed, indicating that alprazolam induced energy metabolism, fatty acid metabolism and amino acid metabolism perturbations in rats. There was no significant difference for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea and uric acid between controls and alprazolam groups. According to the pathological results, alprazolam is not hepatotoxic. Metabolomics could distinguish different alprazolam doses in rats.
      PubDate: 2017-03-16T23:45:40.610015-05:
      DOI: 10.1002/bmc.3956
       
  • The effect of tripterygium glucoside tablet on pharmacokinetics of
           losartan and its metabolite EXP3174 in rats
    • Authors: Yongsheng Hu; Xuexue Zhou, Hui Shi, Wenyu Shi, Shengjie Ye, Hai Zhang
      Abstract: Losartan and tripterygium glucoside tablet (TGT) are often simultaneously used for reducing urine protein excretion in clinic. However, it was unknown whether there is potential herb-drug interaction between losartan and TGT. The aim of this study was to investigate their potential herb-drug interaction, and clarify the mechanism of the effect of TGT on the pharmacokinetics of losartan and its metabolite EXP3174 in rats. The plasma concentration of losartan and EXP3174 were determined by LC-MS, and the main pharmacokinetic parameters were calculated. It was found that Cmax, t1/2, and AUC(0-t) of losartan became larger after co-administration, while the Cmax and AUC(0-t) of EXP3174 became smaller, suggesting that TGT could influence the pharmacokinetics of losartan and EXP3174. The effects of TGT and its main components on the metabolic rate of losartan was further investigated in rat liver microsomes. It was indicated that TGT and its two main ingredients could decrease the metabolic rate of losartan. Therefore, it was speculated that TGT might increase the plasma concentration of losartan and decrease the concentration of EXP3174 by inhibiting the metabolism of losartan. The results could provide references for clinical medication guidance of losartan and TGT to avoid the occurrence of adverse reactions.
      PubDate: 2017-03-16T03:30:41.806644-05:
      DOI: 10.1002/bmc.3973
       
  • Simultaneous determination of piperaquine and its N-oxidated metabolite in
           rat plasma using LC-MS/MS
    • Authors: Huixiang Liu; Meitong Zang, Aijuan Yang, Jianbo Ji, Jie Xing
      Abstract: A sensitive and efficient liquid chromatography tandem mass spectrometry method was firstly developed and validated for the simultaneous determination of piperaquine (PQ) and its N-oxidated metabolite (PQ-M) in plasma. A simple protein precipitation procedure was used for sample preparation. Adequate chromatographic retention was achieved on a C18 column under gradient elution with acetonitrile and 2 mM aqueous ammonium acetate containing 0.15% formic acid and 0.05% trifluoroacetic acid. A triple-quadrupole mass spectrometer equipped with an electrospray source was set up in the positive ion mode and multiple reaction monitoring mode. The method was linear in the range of 2.0-400.0 ng/mL for PQ and 1.0-50.0 ng/mL for PQ-M with suitable accuracy, precision and extraction recovery. The lower limits of detection (LLOD) were established at 0.4 and 0.2 ng/mL for PQ and PQ-M, respectively, using 40 μL of plasma sample. The matrix effect was negligible under the current conditions. No effect was found for co-administrated artemisinin drugs or hemolysis on the quantification of PQ and PQ-M. Stability testing showed that two analytes remained stable under all relevant analytical conditions. The validated method was successfully applied to a pharmacokinetic study performed in rats after a single oral administration of piperaquine (60 mg/kg).
      PubDate: 2017-03-16T02:15:46.114383-05:
      DOI: 10.1002/bmc.3974
       
  • Simultaneous quantification of antofloxacin and its major metabolite in
           human urine by HPLC–MS/MS, and its application to a pharmacokinetic
           study
    • Authors: Yunsu Ma; Qianru Wang, Hongwen Zhang, Lijun Xie, Juan Chen, Mao Huang, Yun Liu, Yuanyuan Wang, Libin Wang, Luning Sun, Ning Ou
      Abstract: This study presents a high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method for the simultaneous determination of antofloxacinin and its main metabolite – N-demethylated metabolite (N-DM) – in human urine. Ornidazole was used as the internal standard. This was a clinical urine recovery study, in which 10 healthy Chinese volunteers were intravenously administered a single 200 mg dose of antofloxacin hydrochloride. Compounds were extracted by albumen precipitation, after which samples were isocratically eluted using a Poroshell 120 SB-C18 column, and were analysed using HPLC–MS/MS under electronic spray ionization positive ion mode. The method was successfully applied in a urine pharmacokinetic study of antofloxacinin, with a detection range of 0.02/0.01 to 200/100 μg/mL (for antofioxacin/N-DM).The average percentages of antofioxacin/N-DM measured in urinary excretion frp, 10 volunteers were 54.9 ± 5.7/8.2 ± 2.5% in 120 h duration.
      PubDate: 2017-03-15T22:05:59.596486-05:
      DOI: 10.1002/bmc.3962
       
  • Development and validation of a high-throughput online solid-phase
           extraction–liquid chromatography–tandem mass spectrometry method for
           the detection of gonyautoxins 1&4 and gonyautoxins 2&3 in human urine
    • Authors: Rebecca Coleman; Sharon W. Lemire, William Bragg, Alaine Garrett, Geovannie Ojeda-Torres, Rebekah Wharton, Elizabeth Hamelin, Jerry Thomas, Rudolph C. Johnson
      Abstract: Paralytic shellfish toxins (PSTs), including gonyautoxins and saxitoxins, are produced by multiple species of microalgae and dinoflagellates, and are bioaccumulated by shellfish and other animals. Human exposure to PSTs typically occurs through ingestion of recreationally harvested contaminated shellfish and results in nonspecific symptomology. Confirmation of exposure to PSTs has often relied on the measurement of saxitoxin, the most toxic congener; however, gonyautoxins (GTXs), the sulfated carbamate derivatives of saxitoxin, may be present in shellfish at higher concentrations. To improve identification of PST exposures, our group has developed an online solid phase extraction hydrophilic interaction liquid chromatography method to identify GTX1–4 in human urine with tandem mass spectrometry. The reportable range varied for each analyte, with all falling within 0.899 and 250 ng/mL in urine with precision 85% accuracy as determined for all quality control samples. This new online method quantitates GTX1–4 following exposures to PSTs, supporting the work of public health authorities.
      PubDate: 2017-03-14T22:26:41.365861-05:
      DOI: 10.1002/bmc.3954
       
  • Elucidation of stress-induced degradation products of mangiferin: Method
           development and validation
    • Authors: Rajneet Kaur Khurana; Satvinder Kaur, Jasleen Kaur, Bhupinder Singh
      Abstract: The degradation behavior of mangiferin, under various ICH Q1A(R2) recommended stress conditions, was studied using an isocratic elution with mobile phase (pH 2.4), composed of acetonitrile and 1% orthophosphoric acid (12:88 v/v) at a flow rate of 1.0 mL/min, with λmax 262 nm. It was suitably adapted for LC–MS studies by replacing with 1% acetic acid (ACN–1% acetic acid; 18:82) and the pH was adjusted to 3.0. Extensive degradation was found to occur during alkaline medium stress studies at 2.31 min of retention time at λmax of 235 nm. The mass spectrum of mangiferin, 3 h after treatment with 0.1 M NaOH, clearly shows the rupture of the tricyclic ring, indicating that a fragment at m/z − 269 was formed. Furthermore, the results were supported by nuclear magnetic resonance as well. However, no degradation was observed in other stress conditions.
      PubDate: 2017-03-13T21:30:37.810499-05:
      DOI: 10.1002/bmc.3935
       
  • Development of a LC-MS/MS method for quantification of two pairs of
           isomeric flavonoid glycosides and other ones in rat plasma: Application to
           pharmacokinetic studies
    • Authors: Sixi Zhang; Yang Xie, Jing Wang, Yanmei Geng, Yu Zhou, Chengxin Sun, Guangshu Wang
      Abstract: An liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous determination of six flavonoid glycosides including isoorientin (1), orientin (2), 2″-O-β-D-xylopyranosyl isoorientin (3), 2″-O-β-D-xylopyranosyl isovitexin (4), 6-C-L-α-arabipyranosyl vitexin (5), and vitexin (6) in rat plasma using isoquercitrin as the internal standard (IS). Plasma samples were prepared by a one-step protein precipitation with acetonitrile. Chromatographic analysis was carried out on a 25-cm C18 column with a gradient mobile phase consisting of acetonitrile and 0.1% aqueous formic acid. Six analytes and IS were detected through electrospray ionization in negative-ion selection reaction monitoring mode. The mass transitions were as follows: m/z 447.2  327.0 for 1, m/z 447.2  327.0 for 2, m/z 579.3  458.9 for 3, m/z 563.0  293.1 for 4, m/z 563.0  353.0 for 5, m/z 431.1  311.1 for 6, and m/z 463.1  300.2 for IS, respectively. Calibration curves exhibited good linearity (r2 > 0.9908) over a wide concentration range for all compounds. Intra-day and inter-day precision (RSD%) at four different levels were both less than 14.2% and the accuracy (RE%) ranged from −11.9% to 12.0%. The extraction recoveries of the six components ranged from 88.2% to 103.6%. The validated assay was successfully applied to the pharmacokinetic studies of the six components in male rat plasma after intravenous administration of total flavonoids of Scorzonera austriaca Wild.
      PubDate: 2017-03-10T10:51:09.585171-05:
      DOI: 10.1002/bmc.3972
       
  • A Simple and Cost Effective Hplc-Uv Method for the Detection of
           Levetiracetam in Plasma/Serum of Patients With Epilepsy
    • Authors: Lynette Engelbrecht; C. J. Grobler, Malie Rheeders
      Abstract: A simple, fast and cost-effective method was developed and validated for the determination of levetiracetam (LEV) in plasma/serum of patients using high performance liquid chromatography (HPLC) with ultra violet detection. The stability of LEV plasma/serum samples over time and in different blood collection tubes was evaluated. Serum/plasma samples were deproteinised by methanol spiked with the internal standard, gabapentin. HPLC was carried out on a Venusil XBP C18, 250 x 4.6 mm, 5 µm column, flow rate of 1.0 ml/min and mobile phase consisting of 50 mM potassium dihydrogen phosphate: acetonitrile at a pH of 5.5. The UV detector was set at 205 nm and 10 µl was injected. Total runtime was 15 minutes. Calibration curves were linear (correlation coefficient = 0.999) over a concentration range of 1 – 60 µg/ml. Relative standard deviation values for both the inter-day and intra-day precision and accuracy were 
      PubDate: 2017-03-10T10:48:42.536931-05:
      DOI: 10.1002/bmc.3969
       
  • A novel assay to determine acetylcholinesterase activity: the application
           potential for screening of drugs against Alzheimer's Disease
    • Authors: Liang Peng; Zhengxing Rong, Hao Wang, Biyun Shao, Lei Kang, Hong Qi, Hongzhuan Chen
      Abstract: Acetycholinesterase (AChE) that regulates hydrolysis of acetylcholine (ACh) in the brain, is an important target for treatment of Alzheimer's disease (AD) featured by ACh deficiency. However, the methods to precisely determine AChE activity are still under development. Here, we created a new method to exploit acetylcholine-d4 (ACh-d4) as a surrogate substrate of ACh and measure product choline-d4 (Ch-d4) via liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay detected activity of AChE present in the normal mouse brain, which is consistent with the standard Ellman assay that determines products spectrophotometrically. In AD mouse models, the result of LC-MS/MS assay showed significant higher AChE activity than that seen in control normal mice, while treatment of AD mice with an AChE inhibitor huperzine A led to partial decreases in AChE activity. Our results suggest that this surrogate-based LC-MS/MS method is a new sensitive and convenient assay for the determination of AChE activity, providing a useful means for screening active compounds that target AChE.
      PubDate: 2017-03-10T10:48:25.370489-05:
      DOI: 10.1002/bmc.3971
       
  • Stability of doripenem in reconstituted solution – thermal and oxidative
           decomposition kinetics and degradation products by LC–MS
    • Authors: Fábio Souza Barbosa; José Pedro Etchepare Cassol, Luiz Alcides das Chagas Batista, Everson Willian Fialho Cordeiro, Marí Castro Santos, Adriana Raffin Pohlmann, Elfrides E. S. Schapoval, Cássia Virginia Garcia, Andreas Sebastian Loureiro Mendez
      Abstract: A ultra-fast liquid chromatography method applied to quantitation of doripenem in powder for injection was validated. Validation parameters were assayed and a rapid analysis was established by a reversed-phase system comprising a C18 column endcapped (50 × 4.0 mm, 2.0 μm), mobile phase consisting of phosphoric acid 0.01% (pH 3.8) and acetonitrile (98:02, v/v) and a flow rate of 0.4 mL min−1. Drug stability was studied through submission to forced conditions, allowing the major degradation products to be detected and the kinetics parameters to be established. Thermal and oxidative degradation were determined, and indicated a kinetic decomposition following first and second order, respectively. The main degradation products were identified by LC–MS analysis, and the results were evaluated in order to suggest the chemical structures corresponding to respective masses and fragmentations. Six compounds were identified, with m/z 411, 427, 437, 634, 650 and 664. All of them resulted from cleavage of β-lactam ring and alcoholic chain and/or dimerization. These experimental results provide valuable information about the stability of doripenem reconstituted solution and procedures for its handling and storage.
      PubDate: 2017-03-10T10:29:52.09915-05:0
      DOI: 10.1002/bmc.3940
       
  • Development and validation of a reversed-phase HPLC method for
           licarbazepine monitoring in serum of patients under oxcarbazepine
           treatment
    • Authors: Elias Begas; Andreas Tsakalof, Efthimios Dardiotis, Georgios Emmanouil Vatidis, Evangelos Kouvaras, Eftihia Konstadinos Asprodini
      Abstract: Licarbazepine is the pharmacologically active metabolite of oxcarbazepine, a drug indicated for the treatment of partial seizures and bipolar disorders. Several HPLC methods have been developed thus far but there is lack of control for interferences from antipsychotic drugs. The aim of the present study was to develop a simple, low-cost and reliable HPLC-UV method for the determination of licarbazepine in human serum in the presence of co-administered antiepileptic, antipsychotic and commonly prescribed drugs. Sample preparation consisted of a single protein precipitation step with methanol. Separation lasted ~9 min on a reversed-phase C18 column using a mobile phase composed of 50 mm sodium-dihydrogen-phosphate-monohydrate/acetonitrile (70:30, v/v) delivered isocratically at 0.9 mL/min and 30°C. Wavelength was 210 nm and calibration curve was linear with r2 0.998 over the range 0.2–50.0 μg/mL. Coefficient of variation was
      PubDate: 2017-03-10T10:29:16.896331-05:
      DOI: 10.1002/bmc.3950
       
  • Chromatographic determination of harmalans in the urine of autistic
           children
    • Authors: Joanna Kałużna-Czaplińska; Jagoda Jóźwik-Pruska, Andrea Axt
      Abstract: This paper presents a new approach to autism – a complex and still enigmatic condition. We present the results of our preliminary research which was based on the detection of the hallucinogenic substance 6- (or 10-)methoxyharmalan in the urine samples of autistic children with the use of chromatographic methods. Additionally, we aim to describe the relationship between the level of tryptophan and harmalan, and the influence of supplementation on the level of this compound. We applied HPLC-UV/vis, HPLC-DAD and LC–MS in order to determine McIsaac's compound in the urine samples obtained from autistic children (n = 132) and healthy individuals (n = 10). The level of tryptophan was quantified with the use of GC–MS. Our research shows the presence of the McIsaac's compound in 110 samples of ASD children contrary to healthy children, where it was not found. No relationship between the level of tryptophan and 6-methoxyharmalan was noticed. The study shows a strong influence of melatonin supplementation on the presence of the McIsaac's compound. We believe that the results of our research can contribute to a better understanding of autism spectrum disorders. Moreover, our findings can form the basis for other studies focused on autism, eventually making it possible to understand its etiology.
      PubDate: 2017-03-09T00:35:30.639192-05:
      DOI: 10.1002/bmc.3951
       
  • LC-MS/MS method for simultaneous determination of flavonoids and physalins
           in rat plasma: application to pharmacokinetic study after oral
           administration of Physalis alkekengi var. franchetii (Chinese lantern)
           extract
    • Authors: Yaqing Guo; Hongxia Liu, Liqin Ding, Mahmood Oppong, Guixiang Pan, Feng Qiu
      Abstract: A rapid and sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of luteolin, luteolin-7-O-glucopyranoside, physalin A, physalin D and physalin L in rat plasma. Scutellarein and dexamethasone were used as the internal standards (IS). Plasma samples were prepared by liquid-liquid extraction with ethyl acetate. The five constituents were separated on an Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm). A gradient elution procedure was used with acetonitrile(A) - 0.1% aqueous formic acid(B). Mass spectrometric detection was performed in negative ion multiple reaction monitoring mode with electrospray ionization (ESI) source. This method showed good linearity (r2 > 0.997) over a concentration range of 2.0-500 ng/mL with a lower limit of quantification of 2.0 ng/mL for all five compounds. The inter- and intra- day accuracy ranged from 91.7 to 104%, and precision (RSD) were less than 6.46% for all analytes. The extraction recoveries of all analytes were higher than 85%. This validated method was successfully applied for the first time to the pharmacokinetic study of five ingredients after oral administration of 70% ethanol extract of Chinese lantern in rats.
      PubDate: 2017-03-08T12:55:27.096961-05:
      DOI: 10.1002/bmc.3970
       
  • Simultaneous determination of eight B-vitamins in rat intestinal perfusate
           to identify effects of osmotic pressures on absorptions
    • Authors: Xiaobo Wang; Jian Xiao, Hui Zhou, Ying Qiu, Hui Peng, Yangyang Sun, Jiwen Zhang, Wei Qian, Lixin Sun
      Abstract: A rapid and accurate HPLC-DAD method was developed and validated to simultaneously determine eight B-vitamins (VBs, namely thiamine, riboflavin, niacinamide, calcium pantothenic, pyridoxine, biotin, folic acid and cyanocobalamin) and phenolsulfonphthalein in rat intestinal perfusate. Chromatographic separation was achieved using an Inertsil ODS-3 column (250 × 4.6 mm i.d., 5 μm) at a temperature of 40°C. Gradient elution mode was applied at the flow rate of 1.0 mL/min with the mobile phase of acetonitrile–30 mm K2HPO4 (pH 5.80). The method was successfully applied to identify the effects of osmotic pressures on the absorption of the VBs. The absorption profiles of single and mixed VBs were also compared. Histological section technology was applied to observe the microstructure of small bowel mucosa after perfusion. The results indicated that each compound possessed a better absorption profile under isotonic conditions than under hypotonic or hypertonic conditions for single or mixed solutions. Compared with single VBs, better absorptions in mixed VBs were observed. Pathological tissue slice test suggested that hypotonic and hypertonic solutions changed or damaged the microstructure of mucosa to varying degrees. Taken together, the investigations indicated that multi-VBs administered orally under isotonic condition could generate fast and complete absorption profiles for VBs.
      PubDate: 2017-03-07T23:55:34.843289-05:
      DOI: 10.1002/bmc.3952
       
  • The establishment of tocopherol reference intervals for Hungarian adult
           population using a validated HPLC method
    • Authors: Gábor Veres; László Szpisjak, Attila Bajtai, Andrea Siska, Péter Klivényi, István Ilisz, Imre Földesi, László Vécsei, Dénes Zádori
      Abstract: Evidence suggests that decreased α-tocopherol (the most biologically active substance in the vitamin E group) level can cause neurological symptoms, most likely ataxia. The aim of the current study was to first provide reference intervals for serum tocopherols in the adult Hungarian population with appropriate sample size, recruiting healthy control subjects and neurological patients suffering from conditions without symptoms of ataxia, myopathy or cognitive deficiency. A validated HPLC method applying a diode array detector and rac-tocol as internal standard was utilized for that purpose. Furthermore, serum cholesterol levels were determined as well for data normalization. The calculated 2.5–97.5% reference intervals for α-, β/γ- and δ-tocopherols were 24.62–54.67, 0.81–3.69 and 0.29–1.07 μm, respectively, whereas the tocopherol/cholesterol ratios were 5.11–11.27, 0.14–0.72 and 0.06–0.22 μmol/mmol, respectively. The establishment of these reference intervals may improve the diagnostic accuracy of tocopherol measurements in certain neurological conditions with decreased tocopherol levels. Moreover, the current study draws special attention to the possible pitfalls in the complex process of the determination of reference intervals as well, including the selection of study population, the application of internal standard and method validation and the calculation of tocopherol/cholesterol ratios.
      PubDate: 2017-03-07T19:40:30.639762-05:
      DOI: 10.1002/bmc.3953
       
  • Development and validation of a HPLC-UV method for the simultaneous
           determination of the antipsychotics clozapine, olanzapine and quetiapine,
           several beta-blockers and their metabolites
    • Authors: Margarete Silva Gracia; Alexandra Köppl, Sandra Unholzer, Ekkehard Haen
      Abstract: A simple, accurate and selective column-switching high performance liquid chromatography (HPLC) method was developed and validated for simultaneous quantification of six beta-blockers (metoprolol MET, timolol TIM, bisoprolol BIS, propranolol PRO, carvedilol CAR and nebivolol NEB), three of their metabolites (α-hydroxy metoprolol α-HMET, N-desisopropyl propranolol DIPRO and 4’-hydroxy carvedilol 4-HCAR), three antipsychotics (olanzapine OLA, clozapine CLO and quetiapine QUE) and three of their metabolites (N-desmethyl olanzapine DMOLA, N-desmethyl clozapine DMCLO and N-desalkyl quetiapine DAQUE) in human serum. After pretreatment on a Merck LiChrospher RP-4 ADS column (25 μm) drugs were separated on a Phenomenex Gemini Phenyl Hexyl 110 A column (250 mm x 4.6 mm, 5 μm) using a gradient mixture of acetonitrile and potassium dihydrogen phosphate buffer pH 3.1 (containing 10 % methanol) as a mobile phase at a flow rate of 1ml/min. The total analysis time was 40 min. For detection of the analytes, four different UV wavelengths were used: 215 nm, 226 nm, 242 nm and 299 nm. The method was validated according to the guidelines of the Society of Toxicology and Forensic Chemistry (GTFCh) in terms of selectivity, linearity, accuracy, precision and stability and successfully applied for the analysis of the 15 described analytes in human serum.
      PubDate: 2017-03-07T05:40:30.207219-05:
      DOI: 10.1002/bmc.3968
       
  • A sensitive quantitative assay for the determination of propafenone and
           two metabolites, 5-hydroxypropafenone and N-depropylpropafenone, in human
           K2EDTA plasma using LC-MS/MS with ESI operated in a positive mode
    • Authors: Harilal Patel; Ashok Ghoghari, Chandrakant Bhatt, Shaival Shah, Anilkumar Jha, Nirmal Desai, Nuggehally R. Srinivas
      Abstract: Propafenone is a potent antiarrhythmic agent; clinically propafenone has been used for a number of cardiac arrhythmias because it possesses multiple modes of action, via beta adrenergic receptor blockade and calcium antagonistic activity. Propafenone (PPF) exhibits extensive saturable presystemic biotransformation (first pass effect) resulting into two active metabolites; 5- hydroxypropafenone (5-OH PPF) formed by CYP2D6 and N-depropylpropafenone (NDP) formed by both CYP3A4 and CYP1A2 enzymes. A specific and sensitive LC-MS/MS method was developed and validated for quantitation of PPF, 5-OH PPF and NDP using turboion spray in a positive ion mode. A solid phase extraction was employed for the extraction from human plasma. Chromatographic separation of analytes was achieved using an ACE-5 C8, (50 x 4.6 mm) column with a gradient mobile phase comprising of ammonium acetate containing 0.01% TFA in purified water and acetonitrile. The retention time was achieved 1.36, 1.23, 1.24 min and 1.34 min for PPF, 5-OH PPF, NDP and IS (carbamazepine), respectively. Quantitation was performed by monitoring MRM transition pairs of m/z 342.30 to m/z 116.20, m/z 358.30 to m/z 116.20, m/z 300.30 to m/z 74.20 and m/z 237.20 to m/z 194.10, respectively. The developed method was validated for various parameters. The calibration curves of PPF and 5-OH PPF showed linearity from 1-500 ng/mL, with a lower limit of quantitation of 1.0 ng/mL and for NDP linearity from 0.1-25 ng/mL with a lower limit of quantitation of 0.1 ng/mL. The bias and precision for intra-and-inter batch assays were less than 10% and 5%, respectively. The developed assay was used to evaluate pharmacokinetic properties of propafenone and its major metabolites in healthy human subjects.
      PubDate: 2017-03-06T03:10:28.069573-05:
      DOI: 10.1002/bmc.3967
       
  • Development and validation of a reversed-phase high-performance liquid
           chromatographic method with solid-phase extraction for the quantification
           of hydrochlorothiazide in ex vivo permeation studies
    • Authors: R. Onnainty; E.M. Schenfeld, M.R. Longhi, M.A. Quevedo, G.E. Granero
      Abstract: Hydrochlorothiazide (HCT) is a diuretic used to treat hypertension. In order to study its intestinal permeation behavior applying an ex vivo methodology, a rapid, sensitive and selective reversed-phase liquid chromatography (RP-HPLC) method coupled with UV detection (RP-HPLC UV) was developed for the analysis of HCT in TC199 culture medium used as mucosal and serosal solutions in the everted rat intestinal sac model. Also, analytical procedures for the quantification of HCT by RP-HPLC with UV detection required a sample preparation step by solid-phase extraction. The method was validated in the concentration range of 8.05 × 10−7 to 3.22 × 10−5 m for HCT. Chromatographic parameters, namely carry-over, lower limit of quantification (1.4491 × 10−7 m), limit of detection (3.8325 × 10−8 m), selectivity, inter- and intraday precision and extraction recovery, were determined and found to be adequate for the intended purposes. The validated method was successfully used for permeability assays across rat intestinal epithelium applying the ex vivo everted rat gut sac methodology to study the permeation behavior of HCT.
      PubDate: 2017-03-02T22:40:46.794208-05:
      DOI: 10.1002/bmc.3943
       
  • Abnormal levels of seven amino neurotransmitters in depressed rat brain
           and determination by HPLC-FLD
    • Authors: Ting Cui; Hong-Mei Qiu, Dan Huang, Qi-Xin Zhou, Xiao-Yan Fu, Hai-Yan Li, Xin-Hui Jiang
      Abstract: The determination of amino acids with actions like neurotransmitters or modulators has been increasingly important for diagnosis in many neuropsychiatric diseases. A rapid and simple high-performance liquid chromatography with fluorescence detection method was developed for simultaneous determination of seven amino acids: aspartate (Asp), glutamate (Glu), serine (Ser), glutamine (Gln), glycine (Gly), taurine (Tau) and γ-aminobutyric` acid (GABA). Homoserine was used as an internal standard. The analysis was performed on a BDS column with methanol and 50 mm sodium acetate solution (pH 6.5) using a simple gradient elution. Several parameters of the developed method were validated including linearity, accuracy, precision, extraction recovery and stability, which were within the acceptable range. The method was successfully applied to determination of real samples: hippocampus and cortex in depressed rats exposed to chronically unpredictable stress in order to study if there existed differences in the seven amino acids levels between depressed rats and control. The results showed that Asp, Gly, Tau and GABA significantly decreased with increasing Gln in the hippocampus of depressed rats, compared with that of the control group, among which obviously lower level of Asp and higher level of Gln in cortex were observed. The analytical method and the results could be useful for clinical diagnosis and further insight into pathophysiological mechanism of depression.
      PubDate: 2017-03-02T22:35:31.455222-05:
      DOI: 10.1002/bmc.3937
       
  • Simultaneous densitometric determination of anthelmintic drug albendazole
           and its metabolite albendazole sulfoxide by HPTLC in human plasma and
           pharmaceutical formulations
    • Authors: Jui J. Pandya; Mallika Sanyal, Pranav S. Shrivastav
      Abstract: A new, simple, accurate and precise high-performance thin-layer chromatographic method has been developed and validated for simultaneous determination of an anthelmintic drug, albendazole, and its active metabolite albendazole, sulfoxide. Planar chromatographic separation was performed on aluminum-backed layer of silica gel 60G F254 using a mixture of toluene–acetonitrile–glacial acetic acid (7.0:2.9:0.1, v/v/v) as the mobile phase. For quantitation, the separated spots were scanned densitometrically at 225 nm. The retention factors (Rf) obtained under the established conditions were 0.76 ± 0.01 and 0.50 ± 0.01 and the regression plots were linear (r2 ≥ 0.9997) in the concentration ranges 50–350 and 100–700 ng/band for albendazole and albendazole sulfoxide, respectively. The method was validated for linearity, specificity, accuracy (recovery) and precision, repeatability, stability and robustness. The limit of detection and limit of quantitation found were 9.84 and 29.81 ng/band for albendazole and 21.60 and 65.45 ng/band for albendazole sulfoxide, respectively. For plasma samples, solid-phase extraction of analytes yielded mean extraction recoveries of 87.59 and 87.13% for albendazole and albendazole sulfoxide, respectively. The method was successfully applied for the analysis of albendazole in pharmaceutical formulations with accuracy ≥99.32%.
      PubDate: 2017-02-27T23:35:30.13833-05:0
      DOI: 10.1002/bmc.3947
       
  • Simultaneous determination of mycophenolic acid and its glucuronide and
           glycoside derivatives in canine and feline plasma by UHPLC-UV
    • Authors: Sol Maiam Rivera; Julianne K. Hwang, Jeniffer E. Slovak, Michael H. Court, Nicolas F. Villarino
      Abstract: Cats and dogs can suffer from multiple autoimmune diseases. Mycophenolic acid (MPA) is a potentially useful immunosuppressant drug in cats and dogs, because of its well-documented efficacy in controlling autoimmune disease in humans. However, the pharmacokinetics and pharmacodynamics in these species remain to be determined. We have developed and validated a sensitive, precise, accurate and reproducible method that provides consistent quantification of MPA and its major derivatives, MPA phenol glucoside and MPA phenol glucuronide, in canine and feline plasma using ultra-high-pressure liquid chromatography coupled to an ultraviolet detector. The main advantages of this novel method include a small sample volume, easy sample preparation, a short chromatographic analysis time and the option to select either phenolphthalein β-d-glucuronide or mycophenolic acid carboxybutoxy ether as internal standard. Results of validation indicate that this analytical method is suitable to study the plasma disposition of MPA and its derivatives in dogs and cats.
      PubDate: 2017-02-27T23:30:47.342272-05:
      DOI: 10.1002/bmc.3942
       
  • Determination of the neuropharmacological drug nodakenin in rat plasma and
           brain tissues by liquid chromatography tandem mass spectrometry:
           Application to pharmacokinetic studies
    • Authors: Yingshi Song; Huiyu Yan, Jingbo Xu, Hongxi Ma
      Abstract: A rapid and sensitive liquid chromatography tandem mass spectrometry detection using selected reaction monitoring in positive ionization mode was developed and validated for the quantification of nodakenin in rat plasma and brain. Pareruptorin A was used as internal standard. A single step liquid–liquid extraction was used for plasma and brain sample preparation. The method was validated with respect to selectivity, precision, accuracy, linearity, limit of quantification, recovery, matrix effect and stability. Lower limit of quantification of nodakenin was 2.0 ng/mL in plasma and brain tissue homogenates. Linear calibration curves were obtained over concentration ranges of 2.0–1000 ng/mL in plasma and brain tissue homogenates for nodakenin. Intra-day and inter-day precisions (relative standard deviation, RSD) were
      PubDate: 2017-02-27T23:30:29.522079-05:
      DOI: 10.1002/bmc.3948
       
  • Application of capillary electrophoresis with capacitively coupled
           contactless conductivity detection (CE-C4D): An update
    • Authors: Abdalla A. Elbashir; Oliver J. Schmitz, Hassan Y. Aboul-Enein
      Abstract: Capacitively coupled contactless conductivity detection (C4D) has appeared as a powerful technique for the detection of compounds lacking chromogenic or fluorogenic group. Since our last review (Biomedical Chromatography 2014; 28: 1502–1506) several new capillary electrophoresis (CE)-C4D methods have been reported. This review provides an update of the most recent utilization of CE-C4D in the field of pharmaceutical, biomedical and food analysis covering the period from February 2014 to October 2016. The use of CE with C4D in the pharmaceutical field has been shown in many papers. Examples illustrate the applicability of CE-C4D in the fields of pharmaceutical, biomedical and food analysis. Finally, general conclusions and perspectives are provided.
      PubDate: 2017-02-27T20:30:37.505072-05:
      DOI: 10.1002/bmc.3945
       
  • Simultaneous determination of wogonin, oroxylin A, schisandrin,
           paeoniflorin and emodin in rat serum by HPLC–MS/MS and application to
           the pharmacokinetic studies
    • Authors: Minting Chen; Suying Wei, Chaohua Luo, Feilong Chen, Shuai Song, Qun Shen, Zhixian Mo, Fenghuan Wei
      Abstract: Wogonin and oroxylin A in Scutellariae Radix, schisandrin in Chinensis fructus, paeoniflorin in Moutan Cortex and emodin in Polygoni Cuspidate Rhizome et Radix are anti–inflammatory active compounds. A method for simultaneous determination of the five compounds in rat was developed and validated using high performance liquid chromatography with tandem mass spectrometry (HPLC–MS/MS). The separation was performed on a Symmetry C18 column (4.6 × 50 mm, 3.5 µm) with acetonitrile and 0.1% formic acid aqueous solution as the mobile phases. The detection was performed using multiple–reaction monitoring with electrospray ionization source in positive–negative ion mode. The calibration curves showed good linearity (r ≥ 0.9955). The lower limit of quantification (LLOQ) was 5 ng/mL for wogonin and schisandrin, 10 ng/mL for oroxylin A and emodin, 15 ng/mL for paeoniflorin, respectively. The relative standard deviations of intraday and interday precisions were lower than 11.49% and 14.28%, respectively. The extraction recoveries and matrix effects were acceptable. The analytes were stable under the experiment conditions. The validated method has been successfully applied to the pharmacokinetics (PK) studies of the five compounds in rats after oral administration of Hu–gan–kan–kang–yuan Capsule. This paper would be a valuable reference for PK studies of Chinese medicine preparations containing the five compounds.
      PubDate: 2017-02-24T21:25:26.552377-05:
      DOI: 10.1002/bmc.3966
       
  • Dissipation kinetics and pre-harvest residue limit of pyriofenone in
           oriental melon (Cucumis melo var. makuwa) grown under regulated climatic
           conditions
    • Authors: Hyung Suk Chung; Md. Humayun Kabir, A. M. Abd El-Aty, Han Sol Lee, Md. Musfiqur Rahman, Byung-Joon Chang, Ho-Chul Shin, Jae-Han Shim
      Abstract: A high-performance liquid chromatography–ultraviolet detection was used to estimate the disappearance rates as well as the pre-harvest residue limits (PHRLs) of pyriofenone in oriental melon (Cucumis melo var. makuwa) grown under greenhouse conditions in two different locations (A and B) in Seongju, Republic of Korea. The identity of the compound in standard solution and representative field incurred samples was confirmed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was validated in terms of linearity, limits of detection and quantification, accuracy (expressed as recovery %), and precision (expressed as relative standard deviation %) for accurate and precise quantitation. Notably, the residual levels of field incurred samples collected over 0 day through 10 days post-application, were below the maximum residue level (MRL = 0.2 mg/kg) established by the Korean Ministry of Food and Drug Safety. Site A showed lower residue levels and a higher decline rate than site B, which might be attributed to seasonal variation (high temperature) and increased metabolic and enzyme profiling in the mature fruits. The half-lives were similar, 4.9 and 4.3 days, at Sites and B, respectively. Using the pre-harvest residue limit, we predicted the residue amounts at ten and five days before harvest, which resulted in concentrations lower than the provisional MRL at harvest time.
      PubDate: 2017-02-23T20:00:23.865725-05:
      DOI: 10.1002/bmc.3965
       
  • Metabolic characterization of the early stage of hepatic fibrosis in rat
           using GC-TOF/MS and multivariate data analyses
    • Authors: Hui Jiang; Jun-mei Song, Peng-fei Gao, Xiu-juan Qin, Shuang-zhi Xu, Jia-fu Zhang
      Abstract: The aim of this study was to explore the changes in the urine metabolic spectrum in rats with the early stage of liver fibrosis using gas chromatography–time of flight/mass spectrometry (GC-TOF/MS), try to search for potential biomarkers and elucidate the probably metabonomic pathogenesis. The early stage of liver fibrosis was established with a single subcutaneous injection of carbon tetrachloride twice each week for 4 weeks continuously. At the end of the experiment, GC-TOF/MS technology with multivariate statistical approaches such as principal component analysis, partial least squares-discriminant analysis and orthogonal partial least squares-discriminant analysis was used to analyze the changes in the metabolic spectrum trajectory and identify potential biomarkers. Twelve potential biomarkers in the model group, such as succinic acid, threonine and lactose, were selected, which indicate that the metabonomic pathogenesis of the early stage of liver fibrosis may be related to disorders of energy metabolism, amino acid metabolism and fatty acid metabolism.
      PubDate: 2017-02-20T20:15:37.757617-05:
      DOI: 10.1002/bmc.3899
       
  • A UPLC–MS/MS method for analysis of vancomycin in human cerebrospinal
           fluid and comparison with the chemiluminescence immunoassay
    • Authors: Shenghui Mei; Jiaqing Wang, Leting Zhu, Ruiling Chen, Xingang Li, Kai Chen, Guangqiang Chen, Jianxin Zhou, Qiang Wang, Zhigang Zhao
      Abstract: Vancomycin (VCM) is clinically used in treating patients with postoperative intracranial infections. The cerebrospinal fluid (CSF) concentration of VCM varies greatly among patients. To guide the dosage regimens, monitoring of VCM in CSF is needed. However a method for analysis of VCM in human CSF is lacking. An ultraperformance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) was developed and validated for analysis of VCM in human CSF, and the agreement of UPLC–MS/MS and chemiluminescence immunoassay (CLIA) in the analysis of CSF VCM was evaluated. The ion transitions were m/z 725.5 > 144.1 for VCM and m/z 455.2 > 308.2 for methotrexate (internal standard). The agreement between UPLC–MS/MS and CLIA was evaluated by Bland–Altman plot in 179 samples. The calibration range of the UPLC–MS/MS method was 1–400 mg/L. The inaccuracy and imprecision were −0.69–10.80% and  0.98). The 95% limit of agreement of the ratio of CLIA to UPLC-MS/MS was 61.66–107.40%. Further studies are warranted to confirm the results.
      PubDate: 2017-02-20T20:05:51.673121-05:
      DOI: 10.1002/bmc.3939
       
  • Novel UHPLC-MS/MS method for the determination of rotigotine in the plasma
           of patients with Parkinson's disease
    • Authors: Susan Mohamed; Roberto Riva, Manuela Contin
      Abstract: A novel ultra-high-pressure liquid chromatography–tandem mass spectrometry method was developed and validated for the determination of the dopamine receptor agonist rotigotine in human plasma. Following liquid–liquid extraction with tert-butyl methyl ether from 500 μL plasma, the chromatographic analysis was performed on a Gemini NX3 column using 5 mm pH 5.0 ammonium acetate–5 mm ammonium acetate in methanol as binary gradient mobile phase, at a flow rate of 0.3 mL/min. The MS/MS ion transitions were 316.00  147.00 for rotigotine and 256.10  211.00 for the internal standard (lamotrigine). The lower limit of quantitation was 50 pg/mL and the linearity was determined from 50 to 2500 pg/mL. The mean recovery was 96.9%. Both intra- and interassay imprecision and inaccuracy were ≤15% at all quality control concentrations. The method was successfully applied to measure morning trough plasma rotigotine concentrations in a series of patients with Parkinson's disease on chronic treatment. The present study describes the first fully validated method for rotigotine determination in human plasma.
      PubDate: 2017-02-20T20:05:48.088164-05:
      DOI: 10.1002/bmc.3944
       
  • Sensitive Quantification of Coixol, a Potent Insulin Secretagogue, in
           Scoparia dulcis Extract using High Performance Liquid Chromatography
           combined with Tandem Mass Spectrometry and UV Detection
    • Authors: Arslan Ali; Faraz Ul Haq, Qamar ul. Arfeen, Khaga Raj Sharma, Achyut Adhikari, Syed Ghulam Musharraf
      Abstract: Diabetes is a major global health problem which requires new studies for its prevention and control. Scoparia dulcis, an herbal product, is widely used for treatment of diabetes. Recent studies demonstrate coixol as a potent and non-toxic insulin secretagogue from S. dulcis. This study focuses on developing two quantitative methods of coixol in Scoparia dulcis methanol-based extracts. Quantification of coixol was performed using high performance liquid chromatography-tandem mass spectrometry (method 1) and high performance liquid chromatography-ultraviolet detection (method 2) with limit of detection of 0.26 pg/μL and 11.6 pg/μL, respectively and with limit of quantification of 0.78 pg/μL and 35.5 pg/μL, respectively. S. dulcis is found rich in coixol content with values of 255.5 ± 2.1 mg/kg (method 1) and 220.4 ± 2.9 mg/kg (method 2). Excellent linearity with determination coefficients higher than 0.999 was achieved for calibration curves from 10 to 7500 ng/mL (method 1) and from 175 to 7500 ng/mL (method 2). Good accuracy (bias 
      PubDate: 2017-02-18T16:25:21.170704-05:
      DOI: 10.1002/bmc.3964
       
  • Long-chain unsaturated fatty acids as possible important metabolites for
           primary angle-closure glaucoma based on targeted metabolomic analysis
    • Authors: Shengzhong Rong; Yang Li, Yue Guan, Lili Zhu, Qiang Zhou, Mucong Gao, Hongzhi Pan, Lina Zou, Dong Chang
      Abstract: Primary angle-closure glaucoma (PACG) is a severe chronic neurodegenerative disease in Asia. Identification of important metabolites associated with PACG is crucial for early intervention and advancing knowledge of the disease mechanism. We applied gas chromatography-mass spectrometry (GC-MS) for targeted metabolomic analysis on serum samples from thirty-eight newly diagnosed PACG patients and forty-eight controls. Palmitoleic acid (PA), linoleic acid (LA), gamma-linolenic acid (GLA) and arachidonic acid (ARA) were identified as important metabolites associated with PACG. PA and GLA were significantly elevated (P 
      PubDate: 2017-02-18T14:00:22.778871-05:
      DOI: 10.1002/bmc.3963
       
  • Comparison of 6-mercaptopurine with 6-thioguanine for the analysis of
           thiopurine S-methyltransferase activity in human erythrocyte by LC-MS/MS
    • Authors: Shenghui Mei; Xindi Li, Xiaoqing Gong, Xiaoyi Zhang, Xingang Li, Li Yang, Leting Zhu, Heng zhou, Yonghong Liu, Anna Zhou, Xinghu Zhang, Zhigang Zhao
      Abstract: Thiopurines (TPDs) are first-line drugs in treating neuromyelitis optica spectrum disorders (NMOSD). Thiopurine S-methyltransferase activity (TPMT), a major determinant of TPDs toxicity, was suggested to be evaluated before TPDs treatment by using 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrate. However, the equivalent of the two substrates in TPMT activity evaluation was unknown, and alternative substrate was required in TPMT activity evaluation in patients who were already taking 6-MP or 6-TG. Before evaluating the agreement of 6-MP and 6-TG in TPMT activity measurement in patients with NMOSD, the affinity of the two substrates for the active center of TPMT should be established. A computer based simulation indicated that 6-MP and 6-TG had the similar affinity for the two active sites of TPMT. According to the guidelines, an LC-MS/MS method was developed and validated to evaluate the TPMT activity in human erythrocyte hemolysate by using 6-MP or 6-TG as substrates via 1 hour incubation at 37 °C. The method was applied in 81 patients with NMOSD. Evaluated by Bland-Altman plot, the 6-methylmercaptopurine (6-MMP) and 6-methylthioguanine (6-MTG) represented TPMT activity were in agreement with each other. Further studies are warranted to confirm the results.
      PubDate: 2017-02-17T15:05:35.102176-05:
      DOI: 10.1002/bmc.3959
       
  • Liquid chromatography high resolution mass spectrometry for the
           determination of baclofen and its metabolites in plasma: Application to
           therapeutic drug monitoring
    • Authors: Laurence Labat; Antonio Goncalves, Ana Rita Marques, Bénédicte Duretz, Bernard Granger, Xavier Declèves
      Abstract: Baclofen is used to manage alcohol dependence. This study describes a simple method using liquid chromatography coupled to high-resolution mass spectrometry (LC-HR-MS) developed in plasma samples. This method was optimized to allow quantification of baclofen and determination of metabolic ratio of its metabolites, an oxidative deaminated metabolite of baclofen (M1) and its glucuronide form (M2). The LC-HR-MS method on Exactive® apparatus is a newly developed method with all the advantages of high resolution in full-scan mode for the quantification of baclofen and detection of its metabolites in plasma. The present assay provides a protein precipitation method starting with 100 μL plasma giving a wide polynomial dynamic range (R2 > 0.999) between 10 and 2000 ng/mL and a lower limit of quantitation of 3 ng/mL for baclofen. Intra- and inter-day precisions were
      PubDate: 2017-02-17T03:00:28.825853-05:
      DOI: 10.1002/bmc.3936
       
  • Preclinical pharmacokinetics of novel trioxane antimalarial drug (99/411)
           – several unanswered questions and development perspectives
    • Authors: Nuggehally R. Srinivas
      PubDate: 2017-02-16T21:05:24.130974-05:
      DOI: 10.1002/bmc.3938
       
  • Comparative pharmacokinetic study of the main components of cortex fraxini
           after oral administration in normal and hyperuricemic rats
    • Authors: Yinan Wang; Min Zhao, Hao Ye, Yizhen Shao, Yongbo Yu, Miao Wang, Chunjie Zhao
      Abstract: Cortex Fraxini is an important traditional Chinese herbal medicine used for the treatment of gout and hyperuricemia. An efficient and rapid ultra-performance liquid chromatography mass spectrometry method was developed and validated for simultaneous quantitation of six coumarins (aesculin, fraxin, aesculetin, fraxetin, sopoletin and 7-hydroxycoumarin) in normal and hyperuricemic rats plasma after oral administration of Cortex Fraxini. The method could successfully be applied for pharmacokinetics studies. The pharmacokinetic behavior of six coumarins in normal and hyperuricemia rats plasma was determined. Results showed that, for some of analytes, the pharmacokinetic parameters (AUC0–t, AUC0–∞, Cmax, Tmax and CL) were significantly different between normal and hyperuricemic rats. The different pharmacokinetic parameters might result from renal impairment or a change of metabolic enzymes in the pathological state. The pharmacokinetic study in pathological state could provide more useful information to guide the clinical use of traditional Chinese herbal medicine.
      PubDate: 2017-02-16T20:30:36.38204-05:0
      DOI: 10.1002/bmc.3934
       
  • Simultaneous determination of the bioactive components in rat plasma by
           UPLC-MS/MS and application in pharmacokinetic studies after oral
           administration of Radix scutellariae extract
    • Authors: Jin-hua Tao; Jun Xu, Shu Jiang, Yong Ling, Dong-geng Wang
      Abstract: A highly sensitive and rapid ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed and validated for simultaneous quantification of the four main bioactive compounds, i.e., baicalin, baicalein, wogonoside and wogonin in rat plasma after oral administration of Radix scutellariae extract. Clarithromycin was used as an internal standard (IS). Plasma samples were processed by protein precipitation with methanol. The separation was performed on an Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 µm) at a flow rate of 0.4 mL/min, using 0.1% formic acid–acetonitrile as mobile phase. The MS/MS ion transit ions monitored were 447.5  270.1 for baicalin, 270.1  168.1 for baicalein, 461.2  284.0 for wogonoside, 284.2  168.1 for wogonin and 748.5  158.1 for IS. Method validation was performed according to Food and Drug Administration guidelines and the results met the acceptance criteria. The lower limit of quantification (LLOQ) achieved was 1.13 ng/mL for baicalin, 1.23 ng/mL for baicalein, 0.82 ng/mL for wogonoside and 0.36 ng/mL for wogonin, respectively. The calibration curves obtained were linear (r > 0.99) over the concentration range approximately 1-1000 ng/mL. The intra- and inter-day precision was less than 15% and the accuracy was within ±14.7%. After validation, this method was successfully applied to a pharmacokinetic study of Radix scutellariae extract.
      PubDate: 2017-02-16T03:26:29.32323-05:0
      DOI: 10.1002/bmc.3961
       
  • Development and Qualification of an LC-MS/MS Method for Investigating the
           Biological Implications of Micelle Entrapped Paclitaxel in Cell Culture
           and Rats
    • Authors: Amal Kaddoumi; Kanwaldeep K. Gill, Khaled Elfakhri, Sami Nazzal
      Abstract: Paclitaxel is a front-line antineoplastic drug used in chemotherapeutic modalities for treatment of various types of malignancies. However, its efficacy is limited by dose related toxicities. In this study, we have explored two important biological aspects of entrapping paclitaxel in PEG2000-DSPE micelles. First, we evaluated the impact of this micellar delivery system on P-glycoprotein (P-gp)-paclitaxel interaction, and we investigated differences in plasma pharmacokinetics of free and micelle entrapped paclitaxel. For quantification of paclitaxel, an LC-MS/MS method was developed. Paclitaxel was extracted from samples using a simple one-step protein precipitation. Chromatographic conditions included a C18 column with a mobile phase consisting of 0.1% formic acid in acetonitrile–water (60:40, v/v) pumped at 1 ml/min. The lower limits of quantitation in both plasma and cell lysate was 1.0 ng/ml. The quantitative linear range was 1–1000 ng/ml. In addition, P-gp efflux studies on free and micellar paclitaxel showed the proficiency of PEG2000-DSPE micelles in evading P-gp mediated efflux thus increasing paclitaxel uptake. Furthermore, the micellar paclitaxel levels were maintained in the body for longer time as compared with taxol, which is desirable for increasing the efficacy of paclitaxel in cancer treatment.
      PubDate: 2017-02-15T23:00:23.364649-05:
      DOI: 10.1002/bmc.3960
       
  • A novel freeze-dried storage and preparation method for the determination
           of mycophenolic acid in plasma by high-performance liquid chromatography
    • Authors: Lei Wang; Wei Qiang, Ying Li, Zeneng Cheng, Mengmeng Xie
      Abstract: Plasma samples were conventionally stored at freezing conditions until the time of detection. Such a technique, when carried out over an extended period, is energy-consuming, in addition, preparation and transportation of stored samples is inconvenient. In this study, a freeze-dried storage and preparation method was proposed to determine the presence of mycophenolic acid (MPA) in plasma. Fresh plasma samples were freeze-dried using a device, and then stored at ambient temperature. After the stored samples were soaked with methanol spiked with the internal standard, high-performance liquid chromatography was conducted to detect MPA. The proposed method was demonstrated to be precise and accurate over the linear range of 0.5-50 µg · mL−1, with both intra- and inter-day precision being less than 7% and biases less than 10%. The freeze-dried samples were stable at ambient temperature for at least 40 d. This method was also successfully applied to the pharmacokinetic study of MPA in healthy volunteers. Pharmacokinetic parameters, such as maximum plasma concentration, time point of maximum plasma concentration, and elimination half-life, among others, were consistent with the results in the published study. This proposed technique was proved to be simple, reproducible, and energy-saving. This approach could also simplify the storage and analysis of samples in clinical and scientific drug research.
      PubDate: 2017-02-15T22:30:23.991437-05:
      DOI: 10.1002/bmc.3958
       
  • Stability studies of potent opioid analgesic, morphine-6-O-sulfate in
           various buffers and biological matrices by HPLC-DAD analysis
    • Authors: Jai Shankar K. Yadlapalli; Zaineb A. F. Albayati, Narasimha R. Penthala, Howard P. Hendrickson, Peter A. Crooks
      Abstract: The 6-O-sulfate ester of morphine, (M6S), has previously been shown to be an analgesic with greater potency and fewer side effects than to morphine. However, being a sulfate ester derivative of morphine, the question exists as to whether this compound is stable in biological fluids and tissues with regard to pH- and esterase-mediated degradation. To date, no studies have focused on the stability profile of M6S across the physiologically relevant pH range of 1.2 – 7.4. In addition, the stability of M6S is not known in rat plasma and rat brain homogenate, or in simulated rat gastric and intestinal fluids. This study determines the stability profile of M6S (utilized as the sodium salt) and demonstrates that M6S is highly stable and resilient to either enzymatic- or pH-dependent hydrolysis in vitro.
      PubDate: 2017-02-15T22:00:26.227864-05:
      DOI: 10.1002/bmc.3957
       
  • Determination of bifonazole and identification of its photocatalytic
           degradation products using UPLC-MS/MS
    • Authors: Agata Kryczyk; Paweł Żmudzki, Urszula Hubicka
      Abstract: The main goal of the presented work was to investigate the effect of ZnO or/and TiO2 on the stability of bifonazole in solutions under UVA irradiation. To this end, a simple and reproducible UPLC method for the determination of bifonazole in the presence of its photocatalytic degradation products was developed. Linearity was studied in the range of 0.0046–0.15 mg mL-1 with a determination coefficient of 0.9996. Bifonazole underwent photocatalytic degradation process under the experimental conditions used. Comparative studies showed that combination of TiO2/ZnO (1:1 w/w) was a more effective catalyst than TiO2 or ZnO with a degradation rate up to 67.57% after 24 hours of irradiation. Further, kinetic analyses indicated that the photocatalytic degradation of bifonazole in the mixture of TiO2/ZnO can be described by a pseudo-first order reaction. Statistical comparison clearly indicated that the presence of TiO2/ZnO also affected the stability of bifonazole from cream preparation after 15 h of UVA exposure (p 
      PubDate: 2017-02-10T05:40:31.304365-05:
      DOI: 10.1002/bmc.3955
       
  • Chemical composition differentiation of Shen-Shuai-Ning granule between
           combined decoction and separated decoction using HPLC-DAD-ESI-QTOF-MS
    • Authors: Jianli Liu; Yu Zhang, Yimeng Hao, Ying Zhao, Yanjiao Li, Rulan Qin, Chongning Lv, Jincai Lu
      Abstract: Shen-Shuai-Ning (SSN) granule, a traditional Chinese medicine formula is widely used in clinical practice for treating chronic renal failure. However, detailed chemical profile about it was unknown. Here, HPLC-ESI-QTOF-MS was employed for the systematic chemical analysis of SSN. A total of 52 compounds were identified and the characteristic ions of compounds were described. Furthermore, chemical consistency between combined decoction and separated decoction of SSN was evaluated using HPLC-DAD. The chemical comparison between two preparations of SSN granule (combined decoction and separated decoction of Coptides Rhizoma) indicated a significant difference in content of many compounds including Salvianolic acid A, Salvianolic acid B, Berberine, Palmatine and Epiberberine. As a result, separated decoction of Coptides Rhizoma would lead to a significantly decrease of depsides in Salviae Miltiorrhizae Radix et Rhizoma while increase of alkaloids in Coptidis Rhizoma.
      PubDate: 2017-02-08T18:00:26.00927-05:0
      DOI: 10.1002/bmc.3949
       
  • The simultaneous UPLC–MS/MS determination of emerging drug combination;
           candesartan and chlorthalidone in human plasma and its application
    • Authors: Bhargav Patel; Arvind G. Jangid, B. N. Suhagia, Nirmal Desai
      Abstract: A novel, precise, sensitive and accurate ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method has been developed for the simultaneous determination of novel drug combination, candesartan (CAN) and chlorthalidone (CHL) in human plasma. Chromatographic separation was achieved on Waters Acquity UPLC BEH C18 (50 mm × 2.1 mm, 1.7 µm). Mobile phase consisting of 1 mM Ammonium acetate in water: acetonitrile (20:80 v/v) was used. The total chromatographic runtime was 1.9 min with retention time for CAN and CHL at 0.7 min and 1.1 min respectively. Ionization and detection of analytes and ISs was performed on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring and negative ionization mode. Quantitation was done to monitor protonated precursor  product ion transition of m/z 439.2  309.0 for CAN, 337.0  189.8 for CHL and 443.2  312.1 for candesartan D4 (CAD) and 341.0  189.8 for chlorthalidone D4 (CHD). The method was validated over a wide dynamic concentration range of 2.0-540.0 ng/mL for candesartan and 1.0-180.0 ng/mL for chlorthalidone. The validated method was successfully applied for the assay of CAN and CHL in healthy volunteers.
      PubDate: 2017-02-08T12:35:23.947226-05:
      DOI: 10.1002/bmc.3946
       
  • Direct inhibition of Re Du Ning Injection and its active compounds on
           human liver cytochrome P450 enzymes by a cocktail method
    • Authors: Danyu Kang; Ting Geng, Yuanpei Lian, Yanjing Li, Gang Ding, Wenzhe Huang, Shiping Ma, Zhenzhong Wang, Zheng Ma, Wei Xiao
      Abstract: The aim of this study was to investigate the direct inhibitory effects of Re Du Ning Injection (RDN) and its active compounds on the major cytochrome P450 enzyme (CYP) isoforms (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) of human liver microsomes by ‘a cocktail method’. The activity of each CYP isform was represented as the formation rate of the specific metabolite from relevant substrate. Then a sensitive and specific ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and validated to simultaneously analyze the seven metabolites. RDN (0.035–2.26 mg/mL) showed a strong inhibitiory effect on CYP2C8, followed by CYP2C9, CYP2B6, CYP2C19, CYP1A2 and CYP3A4. The IC50 value for each enzyme was 0.19, 0.66, 0.72, 1.27, 1.66 and 2.13 mg/mL, respectively. RDN competitively inhibited the activities of CYP1A2 (Ki = 1.22 mg/mL), CYP2B6 (Ki = 0.65 mg/mL) and CYP3A4 (Ki = 0.88 mg/mL); it also exhibited mixed inhibition of CYP2C8, CYP2C9 and CYP2C19 with a Ki value of 0.26, 0.64 and 0.82 mg/mL, respectively. However, the activity of CYP2D6 was not significantly inhibited even by 2.26 mg/mL RDN. Moreover, the data of nine active compounds on the CYPs showed that cryptochlorogenin acid, sochlorogenic acid B and sochlorogenic acid C were the major contributors to the inhibitory effect of RDN on CYP2C8, while the inhibitory effect of RDN on CYP2C9 might be caused by sochlorogenic acid A and sochlorogenic acid C. Moreover, neochlorogenic acid might be the major contributor to the inhibitory effect on CYP2B6. All of the findings suggested that drug–drug interactions may occur and great caution should be taken when RDN is combined with drugs metabolized by these CYPs.
      PubDate: 2017-02-08T01:31:07.572927-05:
      DOI: 10.1002/bmc.3905
       
  • Comparative study on fatty acid composition of olive (Olea europaea L.),
           with emphasis on phytosterol contents
    • Authors: Ali Ozkan; Hassan Y. Aboul-Enein, Muhittin Kulak, Recep Bindak
      Abstract: The present study was designed to determine the fatty acid composition and phytosterol contents of Turkish native olive cultivars, namely Kilis Yağlık and Nizip Yağlık cv. In this context, olive fruits from 34 locations were sampled and then screened for their components in comparison. Fifteen different fatty acids were found in both olive oils. In the order of abundance, the most important ones were oleic acid (18:1) > palmitic acid (16:0) > linoleic acid (18:2) > stearic acid (18:0). Significant differences were observed in the contents of oleic acid (18:1), palmitic acid (16:0), linoleic acid (18:2) but not for stearic acid content in comparison both oils (p 
      PubDate: 2017-02-06T23:20:26.215404-05:
      DOI: 10.1002/bmc.3933
       
  • D-Optimal mixture design optimization of an HPLC method for simultaneous
           determination of commonly used antihistaminic parent molecules and their
           active metabolites in human serum and urine
    • Authors: Selvakumar Kanthiah; Valliappan Kannappan
      Abstract: This study describes a specific, precise, sensitive and accurate method for simultaneous determination of hydroxyzine, loratadine, terfenadine, rupatadine and their main active metabolites cetirizine, desloratadine and fexofenadine, in serum and urine using meclizine as an internal standard. Solid-phase extraction method for sample clean-up and preconcentration of analytes was carried out using Phenomenex Strata-X-C and Strata X polymeric cartridges. Chromatographic analysis was performed on a Phenomenex cyano (150 × 4.6 mm i.d., 5 μm) analytical column. A D-optimal mixture design methodology was used to evaluate the effect of changes in mobile phase compositions on dependent variables and optimization of the response of interest. The mixture design experiments were performed and results were analyzed. The region of ideal mobile phase composition consisting of acetonitrile–methanol–ammonium acetate buffer (40 mm; pH 3.8 adjusted with acetic acid): 18:36:46% v/v/v was identified by a graphical optimization technique using an overlay plot. While using this optimized condition all analytes were baseline resolved in
      PubDate: 2017-02-05T23:20:27.906364-05:
      DOI: 10.1002/bmc.3932
       
  • Simultaneous determination of tanshinol, protocatechuic aldehyde,
           protocatechuic acid, notoginsenoside R1, ginsenoside Rg1 and Rb1 in rat
           plasma by LC–MS/MS and its application
    • Authors: Tingyang Li; Yang Chu, Kaijing Yan, Shuming Li, Xiangyang Wang, Ying Wang, Wei Li, Xiaohui Ma, Jin Yang, Changxiao Liu
      Abstract: Dantonic pill, consisting of Salviae miltiorrhize, Panax notoginseng and Borneol, is a widely used compound Chinese medicine for preventing and treating ischemic cardiovascular diseases in China. In the present study, an original and sensitive method for simultaneous determination of tanshinol (i.e. danshensu), protocatechuic aldehyde, protocatechuic acid, notoginsenoside R1, ginsenoside Rg1 and Rb1 in rat plasma by liquid chromatography–tandem mass spectrometry operated in positive/negative ion switching mode was established and validated. The lower limits of quantification for tanshinol, protocatechuic aldehyde, protocatechuic acid, notoginsenoside R1, ginsenoside Rg1 and Rb1 were 5, 0.5, 1, 0.5, 0.5 and 2 ng/mL, respectively. All of the calibration curves showed good linearity over the investigated concentration range (r > 0.99). Validation results demonstrated that the above compounds were accurately, precisely and robustly quantified in rat plasma. The method was successfully applied to characterize the pharmacokinetic profiles of all six compounds in rats following a single oral administration of Dantonic pill.
      PubDate: 2017-02-05T23:05:30.162381-05:
      DOI: 10.1002/bmc.3889
       
  • Residue analysis and risk assessment of tebuconazole in jujube (Ziziphus
           jujuba Mill)
    • Authors: Xiangwei You; Yiqiang Li, Xiuguo Wang, Jinli Xu, Xiao Zheng, Chengcheng Sui
      Abstract: In this study, a sensitive and reliable analytical method, based on a modified Quick, Easy, Cheap, Effective, Rugged and Safe procedure, was established for determination of tebuconazole in jujube. After extraction with acetonitrile, the samples were cleaned up by dispersive solid-phase extraction with primary secondary amine, and determined by high-performance liquid chromatography tandem mass spectrometry. At fortification levels of 0.01, 0.1 and 2.0 mg kg−1, the average recoveries of tebuconazole in jujube were in the range 97.6–101.9%, with relative standard deviations of 1.5–3.5%. The dissipation and residual levels of tebuconazole in jujube under field conditions were investigated. Tebuconazole dissipated relatively slowly in jujube, with a half-life of 33.0 days. The terminal residue experiments of tebuconazole in jujube were conducted in four locations in China and the risk was evaluated using risk quotients (RQ). RQ values were found to be significantly lower than RQ = 1, indicating that the risk to human health of using the recommended doses of tebuconazole in jujube was not significant. This study could provide guidance for the safe and reasonable use of tebuconazole in jujube and serve as a reference for the establishment of limit of maximum residue in China.
      PubDate: 2017-02-05T23:00:31.372716-05:
      DOI: 10.1002/bmc.3917
       
  • Simultaneous determination of eight bioactive components of Qishen Yiqi
           Dripping Pills in rat plasma using UFLC-MS/MS and its application to a
           pharmacokinetic study
    • Authors: Yaping Shao; Wen Zhang, Ling Tong, Jingyi Huang, Dongxiang Li, Wei Nie, Yan Zhu, Yunfei Li, Tao Lu
      Abstract: In this study, a rapid and reliable ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method was developed and validated for the simultaneous determination of eight active ingredients, including astragaloside IV (AIV), ononin (ONO), tanshinol (TSL), protocatechualdehyde (PCA), protocatechuic acid (PA), salvianolic acid D (SAD), rosmarinic acid (RA), and ginsenoside Rg1 (GRg1), in rat plasma. The plasma samples were pretreated by protein precipitation with acetonitrile. Chromatographic separation was performed on a Waters Acquity UPLC® BEH C18 column (1.7 µm particles, 2.1 × 100 mm).The mobile phase consisted of 0.1% aqueous formic acid (A)-acetonitrile with 0.1% formic acid (B) at a flow rate of 0.4 mL/min. Quantification was performed on a triple quadruple tandem mass spectrometry with electrospray ionization by multiple reaction monitoring both in the negative and positive ion mode. The lower limit of quantification (LLOQ) of TSL was 2.0 ng/mL and the others were 5.0 ng/mL. The extraction recoveries, matrix effects, intra- and inter-day precision and accuracy of eight tested components were all within acceptable limits. The validated method was successfully applied to the pharmacokinetic study of the eight active constituents after intragastric administration of three doses (1.0, 3.0, 6.0 g/kg body weight) of Qishen Yiqi dripping pills to rats.
      PubDate: 2017-02-01T12:40:27.090364-05:
      DOI: 10.1002/bmc.3941
       
  • Cytochrome P450 reaction phenotyping and inhibition and induction studies
           of pinostrobin in human liver microsomes and hepatocytes
    • Authors: Shengnan Tan; Zhimin Dong, Jiashuo Zhang, Thomas Efferth, Yujie Fu, Xin Hua
      Abstract: Pinostrobin (PI, 5-hydroxy-7-methoxyflavanone) is a natural flavonoid known for its rich pharmacological activities. The objective of this study was to identify the human liver cytochrome P450 (CYP450) isoenzymes involved in the metabolism of PI. A single hydoxylated metabolite was obtained from PI after an incubation with pooled human liver microsomes (HLMs). The relative contributions of different CYP450s were evaluated using CYP450-selective inhibitors in HLMs and recombinant human CYP450 enzymes, and the results revealed the major involvement of CYP1A2, CYP2C9 and CYP2E1 in PI metabolism. We also evaluated the ability of PI to inhibit and induce human cytochrome P450 enzymes in vitro. High-performance liquid chromatography and liquid chromatography–tandem mass spectrometry analytical techniques were used to estimate the enzymatic activities of seven drug-metabolizing CYP450 isozymes in vitro. In HLMs, PI did not inhibit CYP 1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 (IC50 > 100 μm). In the induction studies, PI had minimal effects on CYP1A2, CYP2B6and CYP3A4 activity. Based on these results, PI would not be expected to cause clinically significant CYP450 inhibition or induction.
      PubDate: 2017-01-22T23:05:39.538-05:00
      DOI: 10.1002/bmc.3888
       
  • Development of a facile and sensitive HPLC-FLD method via fluorescence
           labeling for triterpenic acid bioavailability investigation
    • Authors: Jinmao You; Di Wu, Mei Zhao, Guoliang Li, Peiwei Gong, Yueyue Wu, Yu Guo, Guang Chen, Xianen Zhao, Zhiwei Sun, Lian Xia, Yongning Wu
      Abstract: Triterpenic acids are widely distributed in many fruits and are known for their medicinal benefits. The study of bioavailability has been an important task for a better understanding of the triterpenic acids. Although many methods based on fluorescence labeling for triterpenic acid determination have been established, these reported methods needed anhydrous conditions, which are not suitable for the convenient study of triterpenic acid bioavailability. Inspired by that, a versatile method, which overcomes the difficulty of the reported methods, has been first developed in this study. The novel method using 2-[12-benzo[b]acridin-5- (12H)-yl]-acetohydrazide (BAAH) as the fluorescence labeling reagent coupled with high-performance liquid chromatography with fluorescence detection was first developed for the study of triterpenic acid bioavailability. Furthermore, the labeling conditions have been optimized in order to achieve the best fluorescence labeling yield. Under the optimal conditions, the quantitative linear range of analytes was 2–1000 ng mL−1, and the correlation coefficients were>0.9998. The detection limits for all triterpenic acid derivatives were achieved within the range of 0.28–0.29 ng mL−1. The proposed method was successfully applied to the study of triterpenic acid bioavailability with excellent applicability and good reproducibility.
      PubDate: 2017-01-17T23:25:31.531543-05:
      DOI: 10.1002/bmc.3894
       
  • Qualitative and quantitative analysis of major constituents from Dazhu
           Hongjingtian capsule by UPLC/Q-TOF-MS/MS combined with UPLC/QQQ-MS/MS
    • Authors: Guang-Da Liu; Yi-Wu Zhao, Yan-Jing Li, Xue-Jing Wang, Hai-Hong Si, Wen-Zhe Huang, Zhen-Zhong Wang, Shi-Ping Ma, Wei Xiao
      Abstract: In this work, a sensitive and efficient method was established and validated for qualitative and quantitative analysis of major bioactive constituents in Dazhu Hongjingtian capsule by liquid chromatography tandem mass spectrometry. A total of 32 compounds were tentatively identified using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Furthermore, 12 constituents, namely gallic acid, 3,4-dihydroxybenzoic acid, salidroside, p-coumaric acid-4-O-β-d-glucopyranoside, bergeninum, 4-hydroxybenzoic acid, 4-hydroxyphenylacetic acid, syringate, 6′′-O-galloylsalidroside, rhodiosin, rhodionin and kaempferol-7-O-α-l-rhamnoside, were simultaneously quantified by the developed ultra-performance liquid chromatography coupled with a triple quadrupole mass spectrometry method in 9 min. All of them were analyzed on an Agilent ZorBax SB-C18 column (3.0 × 100 mm, 1.8 μm) with linear gradient elution of methanol–0.1% formic acid water. The proposed method was applied to analyze three batches of samples with acceptable linearity (R, 0.9979–0.9997), precision (RSD, 1.3–4.7%), repeatability (RSD, 1.7–4.9%), stability (RSD, 2.2–4.9%) and recovery (RSD, 0.6–4.4%) of the 12 compounds. As a result, the analytical method possessing high throughput and sensitivity is suitable for the quality control of Dazhu Hongjingtian capsule.
      PubDate: 2017-01-16T20:05:28.412766-05:
      DOI: 10.1002/bmc.3887
       
  • Simultaneous determination of l-tetrahydropalmatine and its active
           metabolites in rat plasma by a sensitive ultra-high-performance liquid
           chromatography with tandem mass spectrometry method and its application in
           a pharmacokinetic study
    • Authors: Weihui Wang; Jing Liu, Xiaoning Zhao, Yan Peng, Nannan Wang, David Y.W. Lee, Ronghua Dai
      Abstract: A sensitive and reliable ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC–MS/MS) method was developed and validated for simultaneous determination of l-tetrahydropalmatine (l-THP) and its active metabolites l-isocorypalmine (l-ICP) and L-corydalmine (l-CD) in rat plasma. The analytes were extracted by liquid–liquid extraction and separated on a Bonshell ASB C18 column (2.1 × 100 mm; 2.7 μm; Agela) using acetonitrile–formic acid aqueous as mobile phase at a flow rate of 0.2 mL/min in gradient mode. The method was validated over the concentration range of 4.00–2500 ng/mL for l-THP, 0.400–250 ng/mL for l-ICP and 1.00–625 ng/mL for l-CD. Intra- and inter-day accuracy and precision were within the acceptable limits of 0.99 for all analytes. The quantitative method was successfully applied for simultaneous determination of l-THP and its active metabolites in a pharmacokinetic study after oral administration with l-THP at a dose of 15 mg/kg to rats.
      PubDate: 2017-01-16T20:05:25.115997-05:
      DOI: 10.1002/bmc.3903
       
  • Application of a solvent-free solid injection technique coupled with
           GC–MS for discrimination between the secondary metabolites of wild and
           cultivated South Korean medicinal foods
    • Authors: Lieu T. B. Truong; A. M. Abd El-Aty, Hyun Jin Kim, Md. Musfiqur Rahman, Sung-Woo Kim, Ho-Chul Shin, Jae-Han Shim
      Abstract: Solvent-free solid injection was applied to differentiate between wild and cultivated South Korean medicinal foods, including dureup (Aralia elata), deodeok (Codonopsis lanceolata) and doraji (Platycodon grandiflorus). A number of compounds were identified in wild and cultivated dureup (53 and 46), deodeok (47 and 51) and doraji (43 and 38). Secondary metabolites, including butanal,2-methyl-, β-caryophyllene, neoclovene, α-humulene, γ-curcumene, β-bisabolene, and phytol, were identified in dureup with significantly (P 
      PubDate: 2017-01-16T19:55:33.589722-05:
      DOI: 10.1002/bmc.3896
       
  • UPLC-MS/MS method for the determination of tobacco-specific biomarker
           NNAL, tamoxifen and its main metabolites in rat plasma
    • Authors: Wei Xiong; Jiajia Zhao, Ling Wang, Xuehua Jiang
      Abstract: Cigarette smoke is known to interact with tamoxifen-metabolizing enzymes and transporters and potentially affect its treatment outcome. 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanol (NNAL) is an important metabolite of 4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK) because it is frequently used as a biomarker to assess human smoke exposure. In order to study the potential pharmacokinetic interaction between cigarette smoke and tamoxifen in rats a UPLC-MS/MS method for the simultaneous determination of NNAL and tamoxifen along with its metabolites in rat plasma has been developed and validated. Analytes were extracted with methanol and separated on a HSS T3 column by a gradient elution with the mobile phase consisting of acetonitrile and water. The lower limits of quantitation ranged from 0.05 to 0.62 ng/mL. Precisions showed RSD
      PubDate: 2017-01-10T23:05:48.801451-05:
      DOI: 10.1002/bmc.3890
       
  • Rapid analysis of interaction between six drugs and β2-adrenergic
           receptor by injection amount-dependent method
    • Authors: Kaizhu Zeng; Jing Wang, Zhenyu Sun, Qian Li, Sha Liao, Xinfeng Zhao, Xiaohui Zheng
      Abstract: Drug–protein interaction analysis has become a considerable topic in life science which includes clarifying protein functions, explaining drug action mechanisms and uncovering novel drug candidates. This work was to determine the association constants (KA) of six drugs to β2-adrenergic receptor by injection amount-dependent method using stationary phase containing the immobilized receptor. The values of KA were calculated to be (25.85 ± 0.035) × 104 m−1 for clorprenaline, (42.51 ± 0.054) × 104 m−1 for clenbuterol, (6.67 ± 0.008) × 104 m−1 for terbutaline, (33.99 ± 0.025) × 104 m−1 for tulobuterol, (7.59 ± 0.011) × 104 m−1 for salbutamol and (78.52 ± 0.087) × 104 m−1 for bambuterol. This rank order agreed well with the data determined by zonal elution, frontal analysis and nonlinear chromatography, even using different batches of β2-AR column. A good correlation was found between the association constants by the current method and radio-ligand binding assay. Our data indicates that the injection amount-dependent method is a powerful alternative for rapid analysis of ligand–receptor interactions.
      PubDate: 2017-01-10T23:05:30.244794-05:
      DOI: 10.1002/bmc.3897
       
  • Urinary metabolomics of complete Freund's adjuvant-induced hyperalgesia in
           rats
    • Authors: Yang Liu; Hui Chen, Jun Lu, Youshui Jiang, Rui Yang, Songyan Gao, Xin Dong, Wei Chen
      Abstract: The aim of this study was to demonstrate the differences of metabolomics changes in a hyperalgesia model and find potent biomarkers of hyperalgesia. Seven rats were placed in metabolic cages. An emulsion containing 500 μg of Complete Freund's adjuvant (CFA) was used to induce hyperalgesia. Urine samples were collected prior to the injection of CFA and on post-injection days 1, 3 and 7. Ultraperformance liquid chromatography, coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS), was used for a quantitative analysis of urinary metabolic changes in the CFA-induced hyperalgesia model. Differences between the metabolic profiles of the rats in the four groups were analyzed using partial least squares discriminant analysis. Thirty-four potential urine metabolite biomarkers were identified, which changed in a trend similar to the pain threshold. These potential biomarkers were involved in 11 metabolic pathways, as follows: alanine, aspartate, and glutamate metabolism; ascorbate and aldarate metabolism; glycerolipid metabolism; glycerophospholipid metabolism; histidine metabolism; phenylalanine metabolism; sphingolipid metabolism; tryptophan metabolism; tyrosine metabolism; valine, leucine and isoleucine biosynthesis; and vitamin B6 metabolism. These results may improve our understanding of hyperalgesia and provide a basis for the clinical diagnosis of hyperalgesia.
      PubDate: 2017-01-05T21:40:30.947066-05:
      DOI: 10.1002/bmc.3886
       
  • Measurement of caffeine and its three primary metabolites in human plasma
           by HPLC-ESI-MS/MS and clinical application
    • Authors: Feng Chen; Zhe-Yi Hu, Robert B. Parker, S. Casey Laizure
      Abstract: Caffeine is a mild stimulant with significant potential for abuse, being consumed in larger doses with the widespread availability of energy drinks and by novel routes of administration such as inspired powder, oral sprays and electronic cigarettes. How these recent changes in caffeine consumption affecting caffeine disposition and abuse potential is of growing concern. In the study of caffeine disposition in humans, it is common to only measure the caffeine concentration; however, caffeine's three major metabolites (paraxanthine, theobromine and theophylline) retain central nervous system stimulant activity that may contribute to the overall pharmacological activity and toxicity. Therefore, it would be scientifically more rigorous to measure caffeine and its major metabolites in the evaluation of caffeine disposition in human subjects. Herein, we report a method for the simultaneous quantification of caffeine and its three major metabolites in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC-ESI-MS/MS). Human plasma samples were treated by simple protein precipitation and the analytes were separated using a 6 min gradient program. Precision and accuracy were well within in the 15% acceptance range. The simple sample preparation, short runtime, sensitivity and the inclusion of caffeine's major metabolites make this assay methodology optimal for the study of caffeine's pharmacokinetics and pharmacodynamics in human subjects.
      PubDate: 2017-01-04T22:25:46.574706-05:
      DOI: 10.1002/bmc.3900
       
  • Gram (−) microorganisms DNA polymerase inhibition, antibacterial and
           chemical properties of fruit and leaf extracts of Sorbus acuparia and
           Sorbus caucasica var. yaltirikii
    • Authors: Halbay Turumtay; Ahmet Midilli, Emine Akyuz Turumtay, Adem Demir, Emine Kılıçkaya Selvi, Emine Esra Budak, Havva Er, Fatih Kocaimamoglu, Hüseyin Baykal, Ali Osman Belduz, Vagif Atamov, Cemal Sandallı
      Abstract: Investigation of novel plant-based agents might provide alternative antibiotics and thus fight antibiotic resistance. Here, we measured the ability of fruit and leaf extracts of Sorbus aucuparia (Sauc) and endemic Sorbus caucasica var. yaltirikii (Scau) to inhibit nonreplicative (Klenow Fragment-KF and Bacillus Large Fragment-BLF) and replicative (DnaE and PolC) bacterial DNA polymerases along with their antimicrobial, DPPH free radical scavenging activity (RSA), and chemical contents by total phenolic content and HPLC-DAD analysis. We found that leaf extracts had nearly 10-fold higher RSA and 5-fold greater TPC than the corresponding fruit extracts. All extracts had large amounts of chlorogenic acid (CGA) and rutin, while fruit extracts had large amounts of quercetin. Hydrolysis of fruit extracts revealed mainly caffeic acid from CGA (caffeoylquinic acid) and quercetin from rutin (quercetin-3-O-rutinoside), as well as CGA and derivatives of CGA and p-coumaric acid. Plant extracts of Sorbus species showed antimicrobial activity against Gram-negative microorganisms. Scau leaf extracts exhibited strong inhibition of KF activity. Sauc and Scau leaf extracts also strongly inhibited two replicative DNA polymerases. Thus, these species can be considered a potential source of novel antimicrobial agents specific for Gram-negative bacteria.
      PubDate: 2017-01-04T19:35:30.950143-05:
      DOI: 10.1002/bmc.3901
       
  • Chromatographic determination of some biomarkers of liver cirrhosis and
           hepatocellular carcinoma in Egyptian patients
    • Authors: Diaa Osman; Omnia Ali, Manar Obada, Hatem El-Mezayen, Hala El-Said
      Abstract: Metabolomics has been shown to be an effective tool for disease diagnosis, biomarker screening and characterization of biological pathways. A total of 140 subjects were included in this study; urine metabolomes of patients with liver cirrhosis (LC, n = 40), patients with hepatocellular carcinoma (HCC; n = 55) and healthy male subjects (n = 45) as a control group were studied. Gas chromatography/mass spectrometry-based urine metabolomics profiles were investigated for all participants. Diagnostic models were constructed with a combination of marker metabolites, using principal components analysis and receiver operator characteristic curves. A total of 57 peaks could be auto-identified of which 13 marker metabolites (glycine, serine, threonine, proline, urea, phosphate, pyrimidine, arabinose, xylitol, hippuric acid, citric acid, xylonic acid and glycerol) were responsible for the separation of HCC group from healthy subjects. Also, eight markers metabolites (glycine, serine, threonine, proline, citric acid, urea, xylitol and arabinose) showed significant differences between the LC group and healthy subjects. No significant difference was detected between HCC and LC groups regarding all these metabolites. Metabolomic profile using GC–MS established an optimized diagnostic model to discriminate between HCC patients and healthy subjects; also it could be useful for diagnosis of LC patients. However, it failed to differentiate between HCC and LC patients.
      PubDate: 2016-12-28T03:15:53.199032-05:
      DOI: 10.1002/bmc.3893
       
  • Quantification of furosemide in camel plasma by high resolution mass
           spectrometry, application on pharmacokinetics
    • Authors: Ibrahim A. Wasfi; Sayed A. Wajid, B. A. Agha, Asmaa M. Kamel, Nasreen A. Al Biriki, Khaled M. Al Neaimi, Waleed A. Al Ali
      Abstract: We developed and validated a high-resolution liquid chromatography mass spectrometry method for the quantification of furosemide in camel plasma which was used for a pharmacokinetic study in camels. Plasma samples were extracted by supported liquid extraction and furosemide and internal standard (furosemide-D5) were separated on a an Agilent Zorbax XDB C18 column (50 × 2.1 mm i.d., 3.5 μm). Data was acquired in full-scan mode over a mass range of 200–400 Da in negative electrospray mode at a resolution of 70,000. Linear calibration curves were obtained over the concentration ranges of 1.0–10,000 ng/mL. The validated method was then successfully applied in evaluating the pharmacokinetics and metabolites of furosemide in six camels (Camelus dromedarus) and we were able to advice on a withdrawal time of furosemide treatment before racing.
      PubDate: 2016-12-26T19:40:29.116129-05:
      DOI: 10.1002/bmc.3902
       
  • Validated LC–MS/MS method for simultaneous determination of doxorubicin
           and curcumin in polymeric micelles in subcellular compartments of
           MCF-7/Adr cells by protein precipitation–ultrasonic breaking method
    • Authors: Jinling Wang; Ying Li, Wenzhuan Ma, Xiaohui Wang, Pengfei Tu
      Abstract: A specific and sensitive LC–MS/MS with protein precipitation– ultrasonic breaking method has been developed and validated for simultaneous determination of doxorubicin (DOX) and curcumin (Cur) in DOX and Cur co-loaded hyaluronic acid–vitamin E succinatemicelles [(DOX + Cur)–polymeric micelles (PMs)] in subcellular compartments of resistant MCF-7/Adr cells. Sequential extraction of four subcellular protein fractions (cytosolic, membrane/organelle, nucleic and cytoskeleton) was performed directly from MCF-7/Adr cells after incubation with (DOX + Cur)–PMs. An ultrasonic breaking–methanol precipitation method was used for extraction of the fractions, and the micelle breaking efficiency with methanol was 98.1 and 97.6% for DOX and Cur, respectively. The analytes were analyzed using positive electrospray ionization coupled with multiple reaction monitoring. The calibration curves were linear over a concentration range of 0.5–400 ng/mL for DOX and 2–2000 ng/mL for Cur, and the recovery for the two analytes were>85% with negligible matrix effect. The intra-day and inter-day precision was
      PubDate: 2016-12-21T02:02:59.181723-05:
      DOI: 10.1002/bmc.3892
       
  • Simultaneous detection of sulfoxaflor and its metabolites, X11719474 and
           X11721061, in lettuce using a modified QuEChERS extraction method and
           liquid chromatography–tandem mass spectrometry
    • Authors: Sung-Woo Kim; Md. Musfiqur Rahman, A. M. Abd El-Aty, Md. Humayun Kabir, Tae Woong Na, Jeong-Heui Choi, Ho-Chul Shin, Jae-Han Shim
      Abstract: An analytical method has been developed to quantify the residual levels of sulfoxaflor and its metabolites (X11719474 and X11721061) in/on cultivated lettuce grown under greenhouse conditions. Samples were extracted and purified using a quick, easy, cheap, effective, rugged, and safe ‘QuEChERS’ method (original version) following systematic method optimization and were analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Good linearity with coefficient of determination ≥0.9930 was obtained and the limits of detection (LOD) and quantification (LOQ) were in the ranges of 0.003–0.006 and 0.01–0.02 mg/kg, respectively. The recovery rates of both the parent compound and its metabolites (fortified at 10 and 50× the LOQ) estimated from six replicates ranged between 81.9 and 115.5% with a relative standard deviation
      PubDate: 2016-12-19T20:20:26.185996-05:
      DOI: 10.1002/bmc.3885
       
  • Development of a targeted method for quantification of gypenoside XLIX in
           rat plasma, using SPE and LC–MS/MS
    • Authors: Song Guo; Chengxu Sui, Ying Ma
      Abstract: A sensitive, selective and rapid liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the quantification of gypenoside XLIX, a naturally occurring gypenoside of Gynostemma pentaphyllum in rat plasma and then validated according to the US Food and Drug Administration's Guidance for Industry: Bioanalytical Method Validation. Plasma samples were prepared by a simple solid-phase extraction. Separation was performed on a Waters XBridgeTM BEH C18 chromatography column (4.6 × 50 mm, 2.5 μm) using a mobile phase of acetonitrile and water (62.5:37.5, v/v). Gypenoside XLIX and the internal standard gypenoside A were detected in the negative ion mode using selection reaction monitoring of the transitions at m/z 1045.6  913.5 and 897.5  765.4, respectively. The calibration curve was linear (R2 > 0.990) over a concentration range of 10–7500 ng/mL with the lower quantification limit of 10 ng/mL. Intra- and inter-day precision was within 8.6% and accuracy was ≤10.2%. Stability results proved that gypenoside XLIX and the IS remained stable throughout the analytical procedure. The validated LC–MS/MS method was then applied to analyze the pharmacokinetics of gypenoside XLIX after intravenous administration to rats (1.0, 2.0 and 4.0 mg/kg).
      PubDate: 2016-12-14T20:02:25.567584-05:
      DOI: 10.1002/bmc.3898
       
  • Tissue distribution of capilliposide B, capilliposide C and their
           bioactive metabolite in mice using liquid -tandem mass spectrometry
    • Authors: Zhongzhe Cheng; Xing Zhou, Bingying Hu, Wenyi Li, Guiying Chen, Yang Zhang, Jingkui Tian, Lin Zhang, Ming Li, Hongliang Jiang
      Abstract: Lysimachia capillipes Hemsl (Primulaceae), a folk medicinal plant in China, showed significant anti-tumor activities in vivo and in vitro. Capilliposide B (LC-B) and capilliposide C (LC-C) are the main bioactive components in this plant. To explore their tissue distribution, a reliable bioanalytical method for the quantification of LC-B, LC-C and their bioactive metabolite, capilliposide A (LC-A), in mouse tissues was developed and validated. In this study, the tissue distribution profiles of the three compounds were examined after intravenous administration of pure LC-B and oral administration of total saponins of L. capillipes Hemsl extract (LCE) for 10 days. Method validation was conducted over the curve range 10.0–5000 ng/mL for all three analytes in various tissue homogenates. The relative standard deviation of intra-day and inter-day precision of the QC samples was
      PubDate: 2016-12-14T19:55:22.23055-05:0
      DOI: 10.1002/bmc.3895
       
  • Simple extraction method for quantification of phenothiazine residues in
           pork muscle using liquid chromatography–triple quadrupole tandem mass
           spectrometry
    • Authors: Dan Zhang; Jin-A Park, Seong-Kwan Kim, Sang-Hyun Cho, Soo-Min Cho, Jae-Han Shim, Jin-Suk Kim, A. M. Abd El-Aty, Ho-Chul Shin
      Abstract: In this study, an analytical method was developed for quantification of residues of the anthelmintic drug phenothiazine (PTZ) in pork muscle using liquid chromatography–tandem mass spectrometry. Muscles were extracted using 0.2% formic acid and 10 mm ammonium formate in acetonitrile, defatted and purified using n-hexane. The drug was well separated on a Waters XBridge™ C18 analytical column using a binary solvent system consisting of 0.2% formic acid and 10 mm ammonium formate in ultrapure water (A) and acetonitrile (B). Good linearity was achieved over a six-point concentration range in matrix-matched calibration with determination coefficient =0.9846. Fortified pork muscle having concentrations equivalent to and double the limit of quantification (1 ng/g) yielded recovery ranges between 100.82 and 104.03% and relative standard deviations
      PubDate: 2016-12-14T19:50:22.127087-05:
      DOI: 10.1002/bmc.3891
       
 
 
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