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CHEMISTRY (598 journals)                  1 2 3 | Last

Showing 1 - 200 of 735 Journals sorted alphabetically
2D Materials     Hybrid Journal   (Followers: 10)
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: 38)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 18)
ACS Combinatorial Science     Full-text available via subscription   (Followers: 23)
ACS Macro Letters     Full-text available via subscription   (Followers: 24)
ACS Medicinal Chemistry Letters     Full-text available via subscription   (Followers: 39)
ACS Nano     Full-text available via subscription   (Followers: 252)
ACS Photonics     Full-text available via subscription   (Followers: 12)
ACS Synthetic Biology     Full-text available via subscription   (Followers: 23)
Acta Chemica Iasi     Open Access   (Followers: 2)
Acta Chimica Sinica     Full-text available via subscription   (Followers: 1)
Acta Chimica Slovaca     Open Access   (Followers: 1)
Acta Chimica Slovenica     Open Access  
Acta Chromatographica     Full-text available via subscription   (Followers: 9)
Acta Facultatis Medicae Naissensis     Open Access  
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 5)
Acta Scientifica Naturalis     Open Access   (Followers: 2)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 5)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 8)
Adsorption Science & Technology     Full-text available via subscription   (Followers: 5)
Advanced Functional Materials     Hybrid Journal   (Followers: 51)
Advanced Science Focus     Free   (Followers: 3)
Advances in Chemical Engineering and Science     Open Access   (Followers: 57)
Advances in Chemical Science     Open Access   (Followers: 13)
Advances in Chemistry     Open Access   (Followers: 15)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18)
Advances in Drug Research     Full-text available via subscription   (Followers: 22)
Advances in Enzyme Research     Open Access   (Followers: 9)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 8)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 16)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 9)
Advances in Materials Physics and Chemistry     Open Access   (Followers: 21)
Advances in Nanoparticles     Open Access   (Followers: 15)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15)
Advances in Polymer Science     Hybrid Journal   (Followers: 41)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Science and Technology     Full-text available via subscription   (Followers: 12)
African Journal of Bacteriology Research     Open Access  
African Journal of Chemical Education     Open Access   (Followers: 2)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 7)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Al-Kimia : Jurnal Penelitian Sains Kimia     Open Access  
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: 66)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 15)
American Journal of Chemistry     Open Access   (Followers: 27)
American Journal of Plant Physiology     Open Access   (Followers: 14)
American Mineralogist     Hybrid Journal   (Followers: 14)
Analyst     Full-text available via subscription   (Followers: 39)
Angewandte Chemie     Hybrid Journal   (Followers: 179)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 229)
Annales UMCS, Chemia     Open Access   (Followers: 1)
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 4)
Annual Reports in Computational Chemistry     Full-text available via subscription   (Followers: 3)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 4)
Annual Reports Section B (Organic Chemistry)     Full-text available via subscription   (Followers: 8)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 12)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 16)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antiviral Chemistry and Chemotherapy     Hybrid Journal   (Followers: 1)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7)
Applied Spectroscopy     Full-text available via subscription   (Followers: 22)
Applied Surface Science     Hybrid Journal   (Followers: 28)
Arabian Journal of Chemistry     Open Access   (Followers: 6)
ARKIVOC     Open Access   (Followers: 2)
Asian Journal of Biochemistry     Open Access   (Followers: 1)
Atomization and Sprays     Full-text available via subscription   (Followers: 4)
Australian Journal of Chemistry     Hybrid Journal   (Followers: 7)
Autophagy     Hybrid Journal   (Followers: 2)
Avances en Quimica     Open Access   (Followers: 1)
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Biochemistry     Full-text available via subscription   (Followers: 326)
Biochemistry Insights     Open Access   (Followers: 6)
Biochemistry Research International     Open Access   (Followers: 6)
BioChip Journal     Hybrid Journal  
Bioinorganic Chemistry and Applications     Open Access   (Followers: 9)
Bioinspired Materials     Open Access   (Followers: 5)
Biointerface Research in Applied Chemistry     Open Access   (Followers: 2)
Biointerphases     Open Access   (Followers: 1)
Biology, Medicine, & Natural Product Chemistry     Open Access   (Followers: 1)
Biomacromolecules     Full-text available via subscription   (Followers: 19)
Biomass Conversion and Biorefinery     Partially Free   (Followers: 10)
Biomedical Chromatography     Hybrid Journal   (Followers: 6)
Biomolecular NMR Assignments     Hybrid Journal   (Followers: 3)
BioNanoScience     Partially Free   (Followers: 5)
Bioorganic & Medicinal Chemistry     Hybrid Journal   (Followers: 120)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 85)
Bioorganic Chemistry     Hybrid Journal   (Followers: 10)
Biopolymers     Hybrid Journal   (Followers: 18)
Biosensors     Open Access   (Followers: 2)
Biotechnic and Histochemistry     Hybrid Journal   (Followers: 1)
Bitácora Digital     Open Access  
Boletin de la Sociedad Chilena de Quimica     Open Access  
Bulletin of the Chemical Society of Ethiopia     Open Access   (Followers: 2)
Bulletin of the Chemical Society of Japan     Full-text available via subscription   (Followers: 24)
Bulletin of the Korean Chemical Society     Hybrid Journal   (Followers: 1)
C - Journal of Carbon Research     Open Access   (Followers: 3)
Cakra Kimia (Indonesian E-Journal of Applied Chemistry)     Open Access  
Canadian Association of Radiologists Journal     Full-text available via subscription   (Followers: 3)
Canadian Journal of Chemistry     Hybrid Journal   (Followers: 10)
Canadian Mineralogist     Full-text available via subscription   (Followers: 5)
Carbohydrate Research     Hybrid Journal   (Followers: 26)
Carbon     Hybrid Journal   (Followers: 68)
Catalysis for Sustainable Energy     Open Access   (Followers: 7)
Catalysis Reviews: Science and Engineering     Hybrid Journal   (Followers: 8)
Catalysis Science and Technology     Free   (Followers: 7)
Catalysis Surveys from Asia     Hybrid Journal   (Followers: 3)
Catalysts     Open Access   (Followers: 8)
Cellulose     Hybrid Journal   (Followers: 7)
Cereal Chemistry     Full-text available via subscription   (Followers: 5)
ChemBioEng Reviews     Full-text available via subscription   (Followers: 1)
ChemCatChem     Hybrid Journal   (Followers: 8)
Chemical and Engineering News     Free   (Followers: 15)
Chemical Bulletin of Kazakh National University     Open Access  
Chemical Communications     Full-text available via subscription   (Followers: 70)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 25)
Chemical Research in Chinese Universities     Hybrid Journal   (Followers: 3)
Chemical Research in Toxicology     Full-text available via subscription   (Followers: 21)
Chemical Reviews     Full-text available via subscription   (Followers: 184)
Chemical Science     Open Access   (Followers: 22)
Chemical Technology     Open Access   (Followers: 16)
Chemical Vapor Deposition     Hybrid Journal   (Followers: 5)
Chemical Week     Full-text available via subscription   (Followers: 8)
Chemie in Unserer Zeit     Hybrid Journal   (Followers: 56)
Chemie-Ingenieur-Technik (Cit)     Hybrid Journal   (Followers: 24)
ChemInform     Hybrid Journal   (Followers: 8)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 6)
Chemistry & Biology     Full-text available via subscription   (Followers: 30)
Chemistry & Industry     Hybrid Journal   (Followers: 5)
Chemistry - A European Journal     Hybrid Journal   (Followers: 146)
Chemistry - An Asian Journal     Hybrid Journal   (Followers: 15)
Chemistry and Materials Research     Open Access   (Followers: 20)
Chemistry Central Journal     Open Access   (Followers: 4)
Chemistry Education Research and Practice     Free   (Followers: 5)
Chemistry in Education     Open Access   (Followers: 9)
Chemistry International     Hybrid Journal   (Followers: 2)
Chemistry Letters     Full-text available via subscription   (Followers: 42)
Chemistry of Materials     Full-text available via subscription   (Followers: 246)
Chemistry of Natural Compounds     Hybrid Journal   (Followers: 9)
Chemistry World     Full-text available via subscription   (Followers: 22)
Chemistry-Didactics-Ecology-Metrology     Open Access   (Followers: 1)
ChemistryOpen     Open Access   (Followers: 2)
Chemkon - Chemie Konkret, Forum Fuer Unterricht Und Didaktik     Hybrid Journal  
Chemoecology     Hybrid Journal   (Followers: 4)
Chemometrics and Intelligent Laboratory Systems     Hybrid Journal   (Followers: 14)
Chemosensors     Open Access  
ChemPhysChem     Hybrid Journal   (Followers: 10)
ChemPlusChem     Hybrid Journal   (Followers: 2)
ChemTexts     Hybrid Journal  
CHIMIA International Journal for Chemistry     Full-text available via subscription   (Followers: 2)
Chinese Journal of Chemistry     Hybrid Journal   (Followers: 6)
Chinese Journal of Polymer Science     Hybrid Journal   (Followers: 10)
Chromatographia     Hybrid Journal   (Followers: 24)
Clay Minerals     Full-text available via subscription   (Followers: 10)
Cogent Chemistry     Open Access  
Colloid and Interface Science Communications     Open Access  
Colloid and Polymer Science     Hybrid Journal   (Followers: 10)
Colloids and Surfaces B: Biointerfaces     Hybrid Journal   (Followers: 6)
Combinatorial Chemistry & High Throughput Screening     Hybrid Journal   (Followers: 4)
Combustion Science and Technology     Hybrid Journal   (Followers: 19)
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: 11)
Computational Chemistry     Open Access   (Followers: 2)
Computers & Chemical Engineering     Hybrid Journal   (Followers: 9)
Coordination Chemistry Reviews     Full-text available via subscription   (Followers: 3)
Copernican Letters     Open Access   (Followers: 1)
Corrosion Series     Full-text available via subscription   (Followers: 6)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 5)
Croatica Chemica Acta     Open Access  
Crystal Structure Theory and Applications     Open Access   (Followers: 4)
CrystEngComm     Full-text available via subscription   (Followers: 13)
Current Catalysis     Hybrid Journal   (Followers: 2)
Current Metabolomics     Hybrid Journal   (Followers: 5)
Current Opinion in Colloid & Interface Science     Hybrid Journal   (Followers: 9)
Current Opinion in Molecular Therapeutics     Full-text available via subscription   (Followers: 18)
Current Research in Chemistry     Open Access   (Followers: 8)
Current Science     Open Access   (Followers: 64)
Dalton Transactions     Full-text available via subscription   (Followers: 23)
Detection     Open Access   (Followers: 2)
Developments in Geochemistry     Full-text available via subscription   (Followers: 2)
Diamond and Related Materials     Hybrid Journal   (Followers: 12)
Dislocations in Solids     Full-text available via subscription  
Doklady Chemistry     Hybrid Journal  
Drying Technology: An International Journal     Hybrid Journal   (Followers: 4)
Eclética Química     Open Access   (Followers: 1)
Ecological Chemistry and Engineering S     Open Access   (Followers: 3)
Ecotoxicology and Environmental Contamination     Open Access  
Educación Química     Open Access   (Followers: 1)
Education for Chemical Engineers     Hybrid Journal   (Followers: 5)
EJNMMI Radiopharmacy and Chemistry     Open Access  

        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  [1589 journals]
  • Quantification of acyclovir in dermal interstitial fluid and human serum
           by ultra-high-performance liquid chromatography- high resolution tandem
           mass spectrometry for topical bioequivalence evaluation
    • Authors: Denise Schimek; Reingard Raml, Kevin A. Francesconi, Manfred Bodenlenz, Frank Sinner
      Abstract: Time-concentration curves for the topical anti-viral drug acyclovir can provide valuable information for drug development. Open flow microperfusion (OFM) is used for continuous sampling of dermal interstitial fluid but it requires validated methods for subsequent sample analysis. Therefore, we developed a sensitive, selective and high throughput ultra-high-performance liquid chromatography-high resolution tandem mass spectrometry (UHPLC-HR MS/MS) method to determine acyclovir in human dermal interstitial fluid and serum. We validated the method over a concentration range of 0.1 – 25 ng/mL for a sample volume of just 20 μL and employed cation-exchange solid phase extraction in a fully automated sample treatment procedure. Short- and long-term sample stability data and the analysis of 5000 samples from a clinical trial demonstrate the successful application of our method.
      PubDate: 2018-01-19T04:32:55.123184-05:
      DOI: 10.1002/bmc.4194
  • Identification of the absorbed components and metabolites of modified Huo
           Luo Xiao Ling Dan in rat plasma by UHPLC-Q-TOF/MS/MS
    • Authors: Nannan Wang; Xiaoning Zhao, Yiran Li, Congcong Cheng, Jiaxin Huai, Kaishun Bi, Ronghua Dai
      Abstract: To reveal the material basis of Huo Luo Xiao Ling Dan, a sensitive and selective ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC–Q-TOF/MS) method was developed to identify the absorbed components and metabolites in rat plasma after oral administration of HLXLD. The plasma samples were pretreated by liquid-liquid extraction and separated on a Shim-pack XR-ODS C18 column (75 mm × 3.0 mm, 2.2 μm) using a gradient elution program. With the optimized conditions and single sample injection of each positive or negative ion mode, a total of 109 compounds, including 78 prototype compounds and 31 metabolites were identified or tentatively characterized. The fragmentation patterns of representative compounds were illustrated as well. Results indicated that aromatization and hydration were the main metabolic pathways of lactones and tanshinones-related metabolites; demethylation and oxidation were the major metabolic pathways of alkaloid-related compounds; methylation and sulfation were the main metabolic pathways of phenolic acids-related metabolites. It is concluded the developed UHPLC–Q-TOF/MS method with high sensitivity and resolution is suitable for identifying and characterizing the absorbed components and metabolites of HLXLD, and the results will provide essential data for further studying the relationship between the chemical components and pharmacological activity of HLXLD
      PubDate: 2018-01-19T04:16:33.180205-05:
      DOI: 10.1002/bmc.4195
  • Preparation of dummy template-imprinted polymers for the rapid extraction
           of non-steroidal anti-inflammatory drugs residues in aquatic environmental
    • Authors: Ping Guo; Jingjing Zhang, Xiaohui Chen, Longshan Zhao
      Abstract: A molecularly imprinted polymer was synthesized and applied as a sorbent in the solid-phase extraction device. The imprinted polymer was characterized by fourier-transform infrared spectroscopy and scanning electron microscope. The results revealed that imprinted polymer possess sensitive selectivity and reliable adsorption properties for five NSAIDs. The imprinted polymer was successfully applied to the pre-concentration for five NSAIDs in different water samples prior to UPLC-MS/MS. In the early studies, several factors were investigated, including pH adjustment, the kind of elution solvent and the volume of elution solvent. Finally, we found that the pH 5 and an aliquot of 2 mL methanol were suitable for the water samples. The limits of detection and limits of quantitation of five non-steroidal anti-inflammatory drugs varied from 0.007 to 0.480 μg·L-1 and 0.03 to 1.58 μg·L-1, respectively. The spiking recoveries of the target analytes were 50.33-127.64% at the levels of 0.2 μg·L-1, 2 μg·L-1 and 5 μg·L-1. The precision and accuracy of this method showed a great increase compared with traditional solid-phase extraction. The developed method was successfully applied to extraction and analysis of NSAIDs in different water samples with satisfactory results which could help us better understand their environmental fate and risk to ecological health.
      PubDate: 2018-01-19T03:25:34.630662-05:
      DOI: 10.1002/bmc.4193
  • Simultaneous LC-MS/MS bioanalysis of etoposide and paclitaxel in mouse
           tissues and plasma after oral administration of self-microemulsifying drug
           delivery systems
    • Authors: Dan Li; Gang Zhao, Weipeng Ai, Gao Li, Luqin Si, Jiangeng Huang, Yunzhou Chen, Sanlan Wu
      Abstract: In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the anticancer drugs etoposide and paclitaxel in mouse plasma and tissues including liver, kidney, lung, heart, spleen and brain. The analytes were extracted from the matrices of interest by liquid-liquid extraction using DCM: MTBE (1:1, v/v). Chromatographic separation was achieved on an Ultimate XB-C18 column (100 mm × 2.1 mm, 3 μm) at 40 °C and the total run time was 4 min under a gradient elution. Ionization was conducted using electrospray in the positive mode. Stable isotope etoposide-d3 and docetaxel were used as the internal standards (IS). The lower limit of quantitation (LLOQ) of etoposide was 1 ng/g tissue for all tissues and 0.5 ng/mL for plasma. The LLOQ of paclitaxel were 0.4 ng/g tissue and 0.2 ng/mL for all tissues and plasma, respectively. The coefficients of correlation (R2) for all the analytes in the tissues and plasma were greater than 0.99. Both intra-day and inter-day accuracy and precision were satisfactory. This method was successfully applied to measure plasma and tissues drug concentrations in mice treated with etoposide and paclitaxel-loaded self-microemulsifying drug delivery systems.
      PubDate: 2018-01-19T03:10:45.698371-05:
      DOI: 10.1002/bmc.4192
  • Validated UPLC-MS/MS method for quantification of seven compounds in rat
           plasma and tissues: Application to pharmacokinetic and tissue distribution
           studies in rats after oral administration of extract of Eclipta prostrata
    • Authors: Guangyan Du; Lingling Fu, Jun Jia, Xu Pang, Haiyang Yu, Youcai Zhang, Guanwei Fan, Xiumei Gao, Lifeng Han
      Abstract: A rapid, sensitive and specific ultra high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed to investigate the pharmacokinetics and tissue distribution of Eclipta prostrata extract. Rats were orally administrated the 70% ethanol extract of E. prostrata, and their plasma as well as various organs were collected. The concentrations of seven main compounds, including ecliptasaponin IV, ecliptasaponin A, apigenin, 3'-hydroxybiochanin A, luteolin, luteolin-7-O-glucoside, and wedelolactone, were quantified by UPLC–MS/MS through multiple reactions monitoring (MRM) method. The precisions (RSD) of the analytes were all less than 15.00%. The extraction recoveries ranged from 74.65% to 107.45% with RSD ≤ 15.36%. The matrix effects ranged from 78.00% to 118.06% with RSD ≤ 15.04%. To conclude, the present pharmacokinetic and tissue distribution studies provided useful information for the clinical usage of Eclipta prostrata L.
      PubDate: 2018-01-19T02:30:51.954798-05:
      DOI: 10.1002/bmc.4191
  • Intestinal Metabolism of Polygonum Cuspidatum in vitro and in vivo
    • Authors: Jinfeng Fu; Songyan Wu, Min Wang, Yuan Tian, Zunjian Zhang, Rui Song
      Abstract: Rhizoma et Radix Polygoni Cuspidati (RRPC) is commonly prescribed for the treatments of amenorrhea, arthralgia, jaundice and abscess in traditional Chinese medicine. Previous pharmacological studies have indicated that polyphenols are the main pharmacological active ingredients in RRPC. Meanwhile, the poor bioavailability of polyphenols in RRPC implies that those components are probably metabolized by intestinal bacteria before absorption. However, there is rather limited information about RRPC's metabolites produced by intestinal bacteria and the intestinal absorbed constituents. In the present study, the metabolites were characterized after the aqueous extract of RRPC was incubated with the crude enzyme of human intestinal bacteria in vitro. The metabolism characters of glycosides in RRPC were figured out by comparing the metabolism profiles of emodin-8-O-β-D-glucopyranoside and polydatin between aqueous extract of RRPC and equivalent amounts of these two glycosides. The transitional constituents absorbed into blood were investigated in rats via intraduodental administration and portal vein intubation. A total of 38 prototype components and 43 metabolites were detected and characterized in vivo. The overall results demonstrated that the intestinal bacteria played an important role in the metabolism of RRPC, and the main metabolic pathways were hydrolysis in vitro, glucuronidation and sulfation in vivo.
      PubDate: 2018-01-15T18:10:22.125331-05:
      DOI: 10.1002/bmc.4190
  • Determination of isoorientin levels in rat plasma after oral
           administration of Vaccinum bracteatum Thunb. methanol extract by
           high-performance liquid chromatography-tandem mass spectrometry
    • Authors: Min-Ji Kim; Seung-Hwan Kwon, Choon-Gon Jang, Han-Joo Maeng
      Abstract: A simple, sensitive and rapid liquid chromatography tandem mass spectrometry method (LC-MS/MS) was developed and validated for the determination of plasma isoorientin levels in rats. After simple protein precipitation using methanol, chromatographic analysis was performed using a Synergi 4μ polar-RP 80A column (150 mm × 2.0 mm, 4 μm) under isocratic conditions and a mobile phase consisting of 0.1% formic acid in water and methanol (80:20, v/v) at a flow rate of 0.2 mL/min. In positive electrospray ionization mode, the protonated precursor and product ion transitions of isoorientin (m/z 449.0299.1) and of puerarin (the internal standard; m/z 417.1297.1) were acquired by multiple reaction monitoring (MRM). Calibration curves obtained for plasma showed good linearity over the concentration range 1–1000 ng/mL. The lower limit of quantification was 1 ng/mL. Intra- and inter-day precisions were within 8.8% relative standard deviation. Accuracies ranged from 92.1 and 109.7%. The isoorientin stability in rat plasma under typical handling/storage conditions also found to be acceptable. The developed method was applied successfully to a pharmacokinetic study of isoorientin orally administered as the methanol extract of Vaccinium bracteatum Thunb. or administered as pure isoorientin.
      PubDate: 2018-01-15T08:20:25.633989-05:
      DOI: 10.1002/bmc.4188
  • An UPLC-MS/MS method for simultaneous determination of five flavonoids
           from Stellerachamaejasme L. in rat plasma and its application to a
           pharmacokinetic study
    • Authors: Yun-Qing Li; Cheng-Jian Li, Lei Lv, Qing-qing Cao, Xian Qian, Si wei Li, Hui Wang, Liang Zhao
      Abstract: Stellerachamaejasme L. has been used as a Traditional Chinese Medicine for the treatment of scabies, tinea, stubborn skin ulcers, chronic tracheitis, cancer and tuberculosis. A sensitive and selective ultra-high liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of five flavonoids (stelleranol, chamaechromone, neochamaejasmin A, chamaejasmine and isochamaejasmin) of Stellerachamaejasme L. in rat plasma. Chromatographic separation was accomplished on an Agilent Poroshell 120 EC-C18 column (2.1×100 mm, 2.7μm) with gradient elution at a flow rate of 0.4 mL/min and the total analysis time was 7 min. The analytes were detected using multiple reaction monitoring (MRM) in positive ionization mode. The samples were prepared by liquid–liquid extraction with ethyl acetate. The UPLC–MS/MS method was validated for specificity, linearity, sensitivity, accuracy and precision, recovery, matrix effect and stability. The validated method exhibited good linearity(r≥ 0.9956), and the lower limits of quantification ranged from 0.51 to 0.64 ng/mL for five flavonoids. The intra-day and inter-day precision were both less than 10.2%, and the accuracy ranged from -11.79-9.21%. This method was successfully applied to a pharmacokinetic study of five flavonoids in rats after oral administration of ethyl acetate extract of Stellerachamaejasme L.
      PubDate: 2018-01-12T10:30:34.62631-05:0
      DOI: 10.1002/bmc.4189
  • Validation of a chiral LC-MS/MS-ESI method for the simultaneous
           quantification of darolutamide diastereomers in mice plasma and its
           application to a stereoselective pharmacokinetic study in mice
    • Authors: Narayan Balaji; Suresh P. Sulochana, Neeraj Kumar Saini, A. Siva Kumar, Ramesh Mullangi
      Abstract: A simple, selective and reliable LC-MS/MS method was validated for simultaneous quantitation of darolutamide diastereomers in 50 μL mice plasma using warfarin as an internal standard (IS) as per regulatory guidelines. Plasma samples were extracted by liquid-liquid extraction and the chromatographic separation was achieved on a Chiralpak IA column with an isocratic mobile phase 5 mM ammonium acetate:absolute alcohol (20:80, v/v) at a flow rate of 1.0 mL/min. Detection and quantitation was done by MRM mode following the transitions: m/z 397 202 and 307 250 for darolutamide diastereomers and the IS, respectively in the negative ionization mode. The linearity range was 100-2400 ng/mL for each diastereomer. The intra- and inter-day precisions were in the range of 1.78-4.20 and 4.34-14.6; 3.63-4.74 and 4.78-5.15 for diastereomer-1 and diastereomer-2, respectively. Both diastereomers were found to be stable under different stability conditions. The validated method was applied to a pharmacokinetic study in mice. Following oral administration of darolutamide at 10 mg/Kg, maximum concentration in plasma was 4189 and 726 ng/mL for diastereomer-1 and diastereomer-2, respectively. The terminal half-life was found to be ~0.50 h for both the diastereomers. The AUC(0-t) was found to be 18961 ng*h/mL for diastereomer-1 and 1340 ng*h/mL diastereomer-2.
      PubDate: 2018-01-08T07:55:19.087446-05:
      DOI: 10.1002/bmc.4173
  • Determination of cycloserine in microdialysis samples using liquid
           chromatography–tandem mass spectrometry with benzoyl chloride
    • Authors: Wenjing Zhang; Sihui Wan, Lizhi Chen, Xuebing Wang, Zhuo Wang, Yi Huang
      Abstract: A new method for the analysis of cycloserine (4-amino-3-isoxazolidinone, CYC) in rat microdialysis samples has been developed. This method consists of derivatizing the CYC with benzoyl chloride, which transforms primary amines into highly stable derivatives. An attractive feature of this method was that the derivatization reaction is straightforward and can be completed within 10 min. The formed derivative, in contrast to the non-derivatized analyte, exhibited increased chromatographic retention and decreased matrix effects resulting from the co-elution of other components using reversed-phase liquid chromatography and on-line switching. Detection on a quadrupole-linear ion trap mass spectrometer (AB3200 Q-Trap) was performed using electrospray tandem mass spectrometry in multiple reaction monitoring (MRM) mode. Various derivatization parameters were optimized in order to improve chromatographic separation and minimize ion suppression. In particular, the benzoylation reaction was improved to enhance the reproducibility and sensitivity of the chromatographic method. The transition m/z 207.1105.1 was acquired to monitor the CYC derivatization products. The method was fully validated for its sensitivity, selectivity, matrix effect and stability. A good linearity over the selected range (r> 0.99, range=22-2200 mg/L), as well as accuracy and precision within ±7% of the target values, was obtained. The assay described herein was successfully applied to quantitatively measure CYC in the lung and blood of anaesthetized rats.
      PubDate: 2018-01-04T23:45:36.66704-05:0
      DOI: 10.1002/bmc.4187
  • Development and validation of LC-MS/MS method for simultaneous
           determination of sofosbuvir and daclatasvir in human Plasma: Application
           to pharmacokinetic study
    • Authors: Ola M. Abdallah; Ahmed M. Abdel-Megied, Amira S. Gouda
      Abstract: The first simple and highly sensitive Liquid chromatography–tandem mass spectrometry (LC–MS/MS) bioanalytical method was developed and fully validated for the simultaneous determination of newly discovered antiviral drugs namely, Sofosbuvir (SOF) and Daclatasvir (DAC) in human plasma. Tadalafil (TAD) was used as internal standard (IS). SOF, DAC and TAD (IS) were extracted from plasma using liquid-liquid extraction technique with methyl tert-butyl ether. The chromatographic separation was carried out using ZorbaxSB-C18 column (4.6 x 50 mm,5μm) and 5 mM ammonium formate buffer (pH 3.5): acetonitrile (50:50, v/v) as mobile phase in an isocratic elution mode pumped at a flow rate 0.7 mL min-1. The quantitation was performed on API4500 triple quadrupole tandem mass spectrometer with positive electrospray ionization interface in multiple reaction monitoring (MRM) mode. Validation was applied according to FDA guidelines for bio-analytical methodswith respect to linearity, precision, accuracy, selectivity, carry-over, stability and dilution integrity. Linearity was obtained over a concentration range of 0.3-3000 and 3-3000 ng mL-1 for SOF and DAC; respectively by applying weighted least-squares linear regression method (1/x2). The proposed method could be applied successfully in bioequivalence and/or clinical studies for therapeutic drug monitoring (TDM) of patients undergoing dual combination therapy as the latter combination proved more efficacious and powerful tool for the complete treatment of hepatitis C (HCV) genotype 3 within 16 weeks. The suggested method has been applied successfully to pharmacokinetic studies (PK) with excellent assay ruggedness and reproducibility.
      PubDate: 2018-01-03T22:35:52.565839-05:
      DOI: 10.1002/bmc.4186
  • Simultaneous quantification of T4, T3, rT3, 3,5-T2 and 3,3'-T2 in larval
           zebrafish (Danio rerio) as a model to study exposure to polychlorinated
    • Authors: Xiaopeng Chen; Kyla M. Walter, Galen W. Miller, Pamela J. Lein, Birgit Puschner
      Abstract: Environmental toxicants that interfere with thyroid hormone (TH) signaling can impact growth and development in animals and humans. Zebrafish represent a model to study chemically-induced TH disruption, prompting the need for sensitive detection of THs. Simultaneous quantification of 3,3',5-triiodo-L-thyronine (T3), thyroxine (T4), 3,3',5'-triiodo-L-thyronine (rT3), 3,5-diiodo-L-thyronine (3,5-T2), and 3,3'-diiodo-L-thyronine (3,3'-T2) in zebrafish larvae was achieved by ultra-performance liquid chromatography–tandem mass spectrometry in positive ion mode. Solid phase extraction with SampliQ cartridges and derivatization with 3N hydrochloric acid in n-butanol reduced matrix effects. Derivatized compounds were separated on an ACQUITY UPLC BEH C18 column with mobile phases consisting of 0.1% acetic acid in deionized water and 0.1% acetic acid in methanol. The limits of detection ranged from 0.5-0.6 pg injected on column. The method was validated by evaluating recovery (77.1-117.2%), accuracy (87.3-123.9%) and precision (0.5-12.4%) using diluted homogenized zebrafish embryos spiked with all target compounds. This method was then applied to zebrafish larvae collected after 114 hour exposure to polychlorinated biphenyls (PCBs) including PCB 28, PCB 66, PCB 95, or the technical mixture Aroclor 1254. Exposure to PCB 28 and PCB 95 increased the T4:T3 ratio and decreased the T3:rT3 ratio, demonstrating that this method can effectively detect PCB-induced alterations in THs.
      PubDate: 2018-01-03T19:30:22.179893-05:
      DOI: 10.1002/bmc.4185
  • A validated LC-MS/MS method for the determination of senkyunolide I in dog
           plasma and its application to a pharmacokinetic and bioavailability
    • Authors: Jin-Qi Li; Jia-Feng Wang, Jie Li, Shu-han Zhang, Dan He, Rong-Sheng Tong, Shu-Ya She
      Abstract: Senkyunolide I is one of the major bioactive components in herb medicine Ligusticum chuanxiong. The aim of this study was to develop and validate a fast, simple and sensitive LC-MS/MS method for the determination of senkyunolide I in dog plasma. The plasma samples were processed with acetonitrile and separated on a Waters ACQUITY UPLC BEH C18 column (50 × 2.1 mm, 1.7 μm). A mobile phase consisted of 0.1% formic acid aqueous and acetonitrile was delivered at a flow rate of 0.3 mL·min-1. The detection was achieved in the positive selected reaction monitoring (SRM) mode with precursor-to-product transitions at m/z 225.1161.1 for senkyunolide I and at m/z 349.1305.1 for an internal standard. The assay was linear over the tested concentration range, from 0.5 ng·mL-1 to 1000 ng·mL-1, with a correlation coefficient greater than 0.9992. The mean extraction recovery from dog plasma was within the range of 85.78%-93.25%, while the matrix effect of the analyte was within the range of 98.23%-108.89%. The intra- and inter-day precisions (RSD%) were less than 12.12% and the accuracy (RR%) ranged from 98.89% to 104.24%. The validated assay was successfully applied to pharmacokinetic and bioavailability studies of senkyunolide I in dogs. The results demonstrated that 1) senkyunolide I showed short elimination half life (T1/2 < 1 h) in dog; 2) its oral bioavailability was more than 40%; 3) senkyunolide I showed dose-independent pharmacokinetic profiles in dog plasma over the dose range of 1-50 mg·kg-1.
      PubDate: 2018-01-03T07:27:13.777399-05:
      DOI: 10.1002/bmc.4182
  • Detection of monohydroxylated polycyclic aromatic hydrocarbons in urine
           and particulate matter using LC- separations coupled with integrated SPE
           and fluorescence detection or coupled with high resolution time of flight
           mass spectrometry
    • Authors: Jutta Lintelmann; Xiao Wu, Evelyn Kuhn, Sebastian Ritter, Claudia Schmidt, Ralf Zimmermann
      Abstract: A high performance liquid chromatographic (HPLC) method with integrated solid phase extraction (SPE) for the determination of 1-hydroxypyrene and 1-; 2-; 3-; 4- and 9-hydroxyphenanthrene in urine was developed and validated. After enzymatic treatment and centrifugation of 500 μl urine, 100 μl of the sample were directly injected into the HPLC-system. Integrated SPE was performed on a selective, copper phthalocyanine modified packing material. Subsequent chromatographic separation was achieved on a pentafluorophenyl (PFP) core-shell column by using a methanol gradient. For quantification, time programmed fluorescence detection (FLD) was used. Matrix-dependent recoveries were between 94.8 % and 102.4 %, repeatability and reproducibility ranged from 2.2 % to 17.9 %, detection limits lay between 2.6 ng/l and 13.6 ng/l urine. A set of 16 samples from normally exposed adults was analyzed using this HPLC-FLD method. Results were comparable with those reported in other studies.The chromatographic separation of the method was transferred to an ultra high performance liquid chromatography (UHPLC) PFP core-shell column and coupled to a high resolution time of flight mass spectrometer (HR-TOF-MS). The resulting method was used to demonstrate the applicability of LC-HR-TOF-MS for simultaneous target and suspect screening of monohydroxylated polycyclic aromatic hydrocarbons in extracts of urine and particulate matter.
      PubDate: 2018-01-03T07:26:50.75797-05:0
      DOI: 10.1002/bmc.4183
  • Simultaneous analysis of oral anticancer drugs for renal cell carcinoma in
           human plasma using liquid chromatography/electrospray ionization tandem
           mass spectrometry
    • Authors: Shinya Takasaki; Masaki Tanaka, Masafumi Kikuchi, Masamitsu Maekawa, Yoshihide Kawasaki, Akihiro Ito, Yoichi Arai, Hiroaki Yamaguchi, Nariyasu Mano
      Abstract: An analytical method using high performance liquid chromatography/electrospray ionization tandem mass spectrometry has been developed and validated for simultaneous measurement of four tyrosine kinase inhibitors used for renal cell carcinoma and their metabolites in human plasma. Despite their similar structures, it is difficult to measure plasma levels of these compounds simultaneously using optimal MS parameters for each compound because a quantitative range exceeding 50,000-fold is required. To overcome this problem, we used a linear range shift technique using in-source collision-induced dissociation. Linearity ranges of sorafenib, sorafenib N-oxide, sunitinib, N-desethyl sunitinib, axitinib, and pazopanib were 100–10,000, 10–1,000, 1–100, 1–100, 1–100, and 500–50,000 ng/mL, respectively. The intra- and inter-day precision and accuracy were high, and coefficients of variation and relative error were below 10.3% and within ±11.8%, respectively. The matrix effects of all analytes ranged from 87.7% to 114.8%. Extraction recoveries and overall recoveries showed small extraction loss (
      PubDate: 2017-12-28T09:53:00.101633-05:
      DOI: 10.1002/bmc.4184
  • Serum metabolomic of laryngeal cancer based on liquid chromatography
           coupled with quadrupole time-of-flight mass spectrometry
    • Authors: Xiaotao Zhang; Hongwei Hou, Huan Chen, Yong Liu, An Wang, Qingyuan Hu
      Abstract: The discovery of new laryngeal cancer-related metabolite biomarkers could help to facilitate early diagnosis. A serum metabolomics study from laryngeal cancer patients and healthy individuals was conducted by using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Univariate and multivariate statistics were used to discriminate laryngeal cancer patients and healthy individuals. 1-palmitoyl-sn-glycero-3-phosphocholine (LysoPC 16:0), 1-o-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (PAF), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine were found to be significantly different between laryngeal cancer group and healthy group. They are mainly involved in phospholipids catabolism, linoleic acid metabolism, alpha linoleic acid metabolism and arachidonic acid metabolism. The area under the curve of the biomarker combined by two metabolites (LysoPC 16:0 and PAF) was 0.935, the sensitivity was 0.962, and the specificity was 0.825. LysoPC 16:0 and PAF may show diagnostic potential for laryngeal carcinoma.
      PubDate: 2017-12-22T13:00:25.325963-05:
      DOI: 10.1002/bmc.4181
  • New Approach for Determination of the Degradation Products of Fenspiride
           Hydrochloride Found in Oral Liquid Formulations
    • Authors: Bogdan I. Cioroiu; Ioana C. Caba, Irina Prisăcaru, Mona E. Cioroiu, Mihai I. Lazar, Marius Niculaua
      Abstract: Fenspiride hydrochloride (FNS) is used in treating chronic inflammatory diseases, most commonly as a liquid oral solution. FNS produces degradation products along with fenspiride N-oxide (FNO) and 1-phenylethyl-4-hydroxy-4-aminomethyl piperidine hydrochloride (PHAP). We aimed to develop and validate a chromatographic method in order to identify the main degradation products in the presence of other compounds from a liquid preparation. The method used a dual gradient using two buffer solutions; first with pH 4.5 (buffer 1 (pH 4.5)); MeOH 90%:10% (v/v)) and the second with pH 2.9 (buffer 2 (pH 2.9); acetronitrile:methanol (65%:15%:10% v/v/v). As mentioned, there was a modification of the organic mixture, starting with 10% methanol and ending with a mixture of acetonitrile:methanol (15%:10% v/v). The flow-rate was 1.5 mL/min. According to the elution program, experimental conditions started with 100% of solution S1, which decreased to 0% and, simultaneously, solution S2 increased to 100% during the first 10 min and was maintained for a further 5 min. After 15 min, initial conditions were re-established. Linearity interval was 0.5–2 μg mL-1 and minimum correlation coefficient was 0.999. Recovery factor was 100.47–103.17% and the limit of quantification was 0.19–0.332 μg/mL. Intra-day maximum precision was 4.08% for FNS and 2.65% for PHAP. This double-gradient mobile phase produced good specificity in relation to the degradation products of FNS and other constituents of the oral liquid formulation. Forced degradation studies revealed other related substances that were confirmed in mass balance analyses. Degradation products were confirmed in acidic, basic and oxidative media.
      PubDate: 2017-12-19T04:30:20.02129-05:0
      DOI: 10.1002/bmc.4176
  • UPLC-MS/MS based diagnostics for epithelial ovarian cancer using
           fully-sialylated C4-binding protein
    • Authors: Kazuhiro Tanabe; Koji Matsuo, Masaki Miyazawa, Masaru Hayashi, Masae Ikeda, Masako Shida, Takeshi Hirasawa, Ryuichiro Sho, Mikio Mikami
      Abstract: Serum levels of fully sialylated C4-binding protein (FS-C4BP) are remarkably elevated in patients with epithelial ovarian cancer (EOC) and can be used as a marker to distinguish ovarian clear cell carcinoma from endometrioma. This study aimed to develop a stable, robust, and reliable liquid chromatography- hybrid mass spectrometry (UPLC-MS/MS) based diagnostic method that would generalize FS-C4BP as a clinical EOC biomarker. Glycopeptides derived from 20 μL of trypsin-digested serum glycoprotein were analyzed via UPLC equipped with electrospray ionization time-of-flight mass spectrometer. This UPLC-MS/MS-based diagnostic method was optimized for FS-C4BP and validated using sera from 119 patients with EOC and 127 women without cancer. A1958 (C4BP peptide with two fully sialylated biantennary glycans) was selected as a marker of FS-C4BP because its level in serum was highest among FS-C4BP family members. Preparation and UPLC-MS/MS were optimized for A1958, and performance and robustness were significantly improved relative to our previous method. An area under the curve analysis of the FS-C4BP index receiver operating characteristic curve revealed that the ratio between A1958 and A1813 (C4BP peptide with two partially sialylated biantennary glycans) reached 85%. A combination of the FS-C4BP index and carbohydrate antigen-125 levels further enhanced the sensitivity and specificity.
      PubDate: 2017-12-18T16:30:20.15466-05:0
      DOI: 10.1002/bmc.4180
  • Identification of anti-inflammatory active ingredients from Tumuxiang by
           ultra-performance liquid chromatography/quadrupole time-of-flight-MSE
    • Authors: Xia Gao; Yuling Ma, Zhuowei Wang, Ruibin Bia, Pei Zhang, Fangdi Hu
      Abstract: The dried roots of Inula helenium L. (IH) and Inula racemosa Hook f. (IR) are used commonly as folk medicine as “tumuxiang” (TMX). The mixing and sharing of IH and IR in clinical use is a universal phenomenon. Modern pharmacological studies confirmed that IH and IR display anti-inflammatory activities. However, the difference in anti-inflammatory pharmacodynamic substances between these two herbs is still unknown. In the present study, the fingerprints of 18 IH and 9 IR samples were established by using UPLC/QTOF-MSE. A dimethylbenzene-induced mouse ear vasodilation model was applied in evaluating the anti-inflammatory properties of all 27 samples. Then, the spectrum-efficacy model between chemical characteristic peaks and anti-inflammatory activities was investigated using principal component regression (PCR) and partial least squares (PLS). Finally, the combination of UNIFI Scientific Information System with a library search of traditional Chinese medicines (TCMs) was employed to automatically characterize the peaks. UNIFI identified a total of 80 chemical components. Among the components, the 53 characteristic peaks had correlation with anti-inflammatory activities, pointed to phenolic and organic acids as primary anti-inflammatory ingredients of TMX. This approach can efficiently and intelligently facilitate the identification of bioactive components from TCMs.
      PubDate: 2017-12-18T07:06:16.770018-05:
      DOI: 10.1002/bmc.4179
  • HPLC-MS/FMS analysis of anthocyanins in human plasma and urine using
           protein precipitation and dilute-and-shoot sample preparation methods,
    • Authors: Junguo Liu; Jiuxue Song, Karen Huang, Deborah Michel, Jim Fang
      Abstract: A high performance liquid chromatography tandem-mass spectrometry (HPLC-MS/MS) method has been developed to analyze anthocyanins in urine and plasma to further understand their absorption, distribution, metabolism and excretion. The method employed a Synergi RP-Max column (250 x 4.6 mm, 4 μm) and an API 4000 mass spectrometer. A gradient elution system consisted of mobile phase A (water/1% formic acid) and mobile phase B (acetonitrile) with a flow rate of 0.60 ml/min. The gradient was initiated at 5% B, increased to 40% B at 15 min, and then increased to 100% B at 22 min. The analysis of anthocyanins presents a challenge because of the poor stability of anthocyanins during sample preparation, especially during solvent evaporation. In this method, the degradation of anthocyanins was minimized using protein precipitation and dilute-and-shoot and sample preparation methods for plasma and urine, respectively. No interferences were observed from endogenous compounds. The method has been used to analyze anthocyanin concentrations in urine and plasma samples from volunteers administered saskatoon berries. Cyanidin-3-galactoside, cyanidin-3-glucoside, cyanidin-3-arabinoside, cyanidin-3-xyloside, and quercetin-3-galactoside, the five major flavonoids components in saskatoon berries, were identified in plasma and urine samples.
      PubDate: 2017-12-18T06:05:34.612176-05:
      DOI: 10.1002/bmc.4177
  • Development of a Validated Liquid Chromatographic Method for
           Quantification of Sorafenib Tosylate in the Presence of Stress-Induced
           Degradation Products and in Biological Matrix employing Analytical Quality
           by Design (AQbD) Approach
    • Authors: Teenu Sharma; Rajneet Kaur Khurana, Atul Jain, O.P. Katare, Bhupinder Singh
      Abstract: The current research work envisages AQbD-enabled development of a simple, rapid, sensitive, specific, robust and cost-effective stability indicating reversed phase high performance liquid chromatographic (RP-HPLC) method for determining stress-induced forced degradation products of sorafenib tosylate (SFN). An Ishikawa fish bone diagram was constructed to embark upon analytical target profile (ATP) and critical analytical attributes (CAAs) i.e., peak area, theoretical plates, retention time (Rt) and peak tailing. Factor screening using Taguchi orthogonal arrays and quality risk assessment studies carried out using failure mode effect analysis (FMEA) aided the selection of critical method parameters (CMPs) i.e., mobile phase ratio and flow rate potentially affecting the chosen CAAs. Systematic optimization using response surface methodology (RSM) of the chosen CMPs was carried out employing a 2 factor-3 level-13 run, face-centred cubic design. A method operable design region (MODR) was earmarked providing optimum method performance using numerical and graphical optimization. The optimum method employed mobile phase composition consisting of acetonitrile and water (containing orthophosphoric acid, pH 4.1) in 65:35 v/v at a flow rate of 0.8 mL/min with UV detection at 265 nm using a C18 column. RSM validation studies confirmed high efficiency and sensitivity of the developed method for analysis of SFN in mobile phase as well as in human plasma matrix. The forced degradation studies were conducted under different recommended stress conditions as per ICH Q1A (R2). Mass spectroscopy studies showed that SFN degrades in strongly acidic, alkaline and oxidative hydrolysis conditions at elevated temperature, while drug was per se found to be photostable. Oxidative hydrolysis using 30% H2O2 showed maximum degradation with products at Rt of 3.35, 3.65, 4.20 and 5.67 minutes. Absence of any significant change in the retention time of SFN and degradation products, formed under different stress conditions, ratified selectivity and specificity of the systematically developed method.
      PubDate: 2017-12-15T08:32:39.4729-05:00
      DOI: 10.1002/bmc.4169
  • Simultaneous quantification of multiple components in rat plasma by
           UPLC-MS/MS and pharmacokinetic study after oral administration of Huangqi
    • Authors: Jia-Kai Zeng; Yuan-Yuan Li, Tian-Ming Wang, Jie Zhong, Jia-Sheng Wu, Ping Liu, Hua Zhang, Yue-Ming Ma
      Abstract: A rapid, sensitive, and accurate UPLC-MS/MS method was developed for the simultaneous quantification of components of Huangqi decoction (HQD), such as calycosin-7-O-β-D-glucoside, calycosin-glucuronide, liquiritin, formononetin-glucuronide, isoliquiritin, liquiritigenin, ononin, calycosin, isoliquiritigenin, formononetin, glycyrrhizic acid, astragaloside IV, cycloastragenol, and glycyrrhetinic acid, in rat plasma. After plasma samples were extracted by protein precipitation, chromatographic separation was performed with a C18 column, using a gradient of methanol and 0.05% acetic acid containing 4 mM ammonium acetate as the mobile phase. Multiple reaction monitoring scanning was performed to quantify the analytes, and the electrospray ion source polarity was switched between positive and negative modes in a single run of 10 min. Method validation showed that specificity, linearity, accuracy, precision, extraction recovery, matrix effect, and stability for 14 components met the requirements for their quantitation in biological samples. The established method was successfully applied to the pharmacokinetic study of multiple components in rats after intra-gastric administration of HQD. The results clarified the pharmacokinetic characteristics of multiple components found in HQD. This research provides useful information for understanding the relation between the chemical components of HQD and their therapeutic effects.
      PubDate: 2017-12-15T03:05:44.411236-05:
      DOI: 10.1002/bmc.4178
  • Purification of angiotensin converting enzyme from human plasma and
           investigation of the effect of some active ingredients isolated from
           Nigella sativa L. extract on the enzyme activity
    • Authors: Zehra Basi; Vedat Turkoglu
      Abstract: In the present study, one-step purification of angiotensin converting enzyme (ACE, peptidyldipeptidase A, EC, responsible from regulation of blood pressure, was achieved using affinity chromatography from human plasma. The enzyme was purified 12860-fold with a spesific activtiy of 5080 EU/mg.protein. Optimum temperature and pH were determined for the enzyme as 35-40 °C and pH 7.4-7.5, respectively. The purity of ACE was determined by SDS-PAGE and the enzyme showed two bands at 60 kDa and 70 kDa on the gel. The native molecular weight of ACE was found to be 260 kDa by gel filtration chromatography, demonstrating that the enzyme has a heterodimeric structure. Natural fatty acids of Nigella sativa (Ranunculaceae) were isolated by means of column chromatography. The structure of these compounds was determined using NMR and GC-MS. The results showed that high amounts of linoleic, oleic, and palmitic acids were isolated from the plant. The effect of six fractions (Fr 1-6) on ACE activity was examined. Fr 3 increased the ACE activity while the other fractions decreased the enzyme activity. The concentrations of the fractions inhibiting the half of maximum activity of the enzyme (IC50) were calculated as 1.597 mg/mL for Fr 1, 0.053 mg/mL for Fr 2, 0.527 mg/mL for Fr 4, 0.044 mg/mL for Fr 5, and 0.136 mg/mL for Fr 6 using Lineweaver-Burk graph.
      PubDate: 2017-12-15T03:05:20.028224-05:
      DOI: 10.1002/bmc.4175
  • The issue of HPLC determination of endogenous lipoic acid in human plasma
    • Authors: Soňa Sechovcová; Pavla Královcová, Roman Kanďár, Karel Ventura
      Abstract: Lipoic acid (LA) is used extensively as a therapeutic agent for the treatment of various diseases. Many methods have been reported for the determination of LA plasma levels and its metabolites after its supplementation, but available information concerning endogenous plasma levels is still rare. Studies, which directly focused on determining the endogenous plasma levels, provided highly controversial results, less than 4.9 nmol/L or 143.7 – 197.0 nmol/L.The main aim of this study was to verify the levels of free LA in the plasma of 40 individuals (17 women, 23 men). This group was non-supplemented with LA and met the conditions for incorporation into the blood donors register. We measured the levels of LA using an HPLC method with very sensitive coulometric detection after previous sample preparation including deproteination and solid phase extraction with phenyl cartridge.Our limit of detection was 1.85 nmol/L and was better than the LODs in studies, which directly focused on determining the endogenous plasma levels of LA, 2.4 nmo/L and 4.9 nmol/L respectively. However, the levels of free LA in the plasma of non-supplemented voluntary blood donors were not detectable in all cases. The presented results of our study show that endogenous concentrations of LA are less than 1.85 nmol/L.
      PubDate: 2017-12-14T11:25:18.921587-05:
      DOI: 10.1002/bmc.4172
  • LC-MS/MS profiling of polyphenol-enriched leaf, stem, and root extracts of
           Korean Humulus japonicus Siebold & Zucc and determination of their
           antioxidant effects
    • Authors: Jin Young Choi; Kebede Taye Desta, Soo Jung Lee, Yun-Hi Kim, Sung Chul Shin, Gon-Sup Kim, Sung Joong Lee, Jae-Han Shim, Ahmet Hacımüftüo, A.M. Abd El-Aty
      Abstract: Polyphenols from ethyl acetate extracts from the leaves, stems, and roots of Korean Humulus japonicus were comprehensively profiled using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). A total of 36 polyphenols were detected, of which 26 were structurally characterized based on their [M-H]- peak, MS/MS fragmentation pattern, UV-Vis absorption, and published data. Validation data provided satisfactory results for the evaluated parameters. The determination coefficients (R2) exceeded or equal to 0.9812. The limits of detection (LODs) and quantification (LOQs) were 0.017–0.573 and 0.056–1.834 mg/L, respectively, indicating good performance limits. The accuracy (expressed as percent recovery) at 50 and 100 mg/L was 71.4–99.7 and 75.1–105.1%, with precision (expressed as relative standard deviations (RSDs)) of 1.5–7.3 and 0.8–4.1%, respectively, indicating acceptable accuracy and precision values. The leaves were rich in total polyphenols (3089.9 ± 6.4 mg/kg of fresh sample) followed by the stems (1313.9 ± 6.4 mg/kg of fresh sample), and roots (655.2 ± 2.7 mg/kg of fresh sample). Antioxidant activity, determined by α,α-diphenyl-β-picrylhydrazyl (DPPH•), 2–2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+) scavenging activity, and ferric reducing antioxidant power (FRAP) assay, revealed the lowest EC50 value for the leaf extracts, indicating a higher scavenging activity in this tissue followed by the roots and stems. Overall, the results indicated that H. japonicus is rich in polyphenols and could be a potential alternative to Humulus lupulus (Hop plant) in the brewery industry.
      PubDate: 2017-12-14T10:56:26.774846-05:
      DOI: 10.1002/bmc.4171
  • Chromatographic Methods in HIV Medicine: Application to Therapeutic Drug
    • Authors: Timothy L. Archibald; Derek E. Murrell, Stacy D. Brown
      Abstract: HIV antiretroviral therapy spans several different drug classes, meant to combat various aspects of viral infection and replication. Many authors have argued the benefits of therapeutic drug monitoring (TDM) for the HIV-patient including compliance assurance and assessment of appropriate drug concentrations; however, the array of drug chemistries and combinations makes TDM an arduous task. HPLC-UV and LC-MS/MS are both frequent instruments for the quantification of HIV drugs in biological matrices with investigators striving to balance sensitivity and affordability. Plasma, the dominant matrix for these analyses, is prepared using protein precipitation, liquid-liquid extraction, or solid-phase extraction depending on the specific complement of analytes. Despite the range of polarities found in drug classes relevant to HIV therapeutics, most chromatographic separations utilize a hydrophobic column (C18). Additionally, as the clinically relevant samples for these assays are infected with HIV, along with possible co-infections, another important aspect of sample preparation concerns viral inactivation. Although not routine in clinical practice, many published analytical methods from the previous two decades have demonstrated the ability to conduct TDM in HIV patients receiving various medicinal combinations. This review summarizes the analytical methods relevant to TDM of HIV drugs; while highlighting respective challenges.
      PubDate: 2017-12-14T10:05:40.036678-05:
      DOI: 10.1002/bmc.4170
  • Biomedical Chromatography 2018
    • Authors: Michael G. Bartlett
      PubDate: 2017-12-13T02:51:47.383812-05:
      DOI: 10.1002/bmc.4152
  • Issue information
    • Abstract: No abstract is available for this article.
      PubDate: 2017-12-13T02:51:45.639388-05:
      DOI: 10.1002/bmc.4070
  • A Simple and Rapid HPLC-UV Method for the Determination of Retigabine in
           Human Plasma
    • Authors: Valentina Franco; Katia Baruffi, Giuliana Gatti, Roberto Marchiselli, Cinzia Fattore, Maria Paola Canevini, Francesca Crema, Emilio Perucca
      Abstract: A simple and rapid high-performance liquid chromatographic method with ultraviolet detection was developed for the quantitative determination of retigabine, known also as ezogabine, in human plasma. The assay uses a simple solid phase extraction for sample preparation and direct injection of the extract into the chromatograph. Flupirtine is used as an internal standard. Chromatographic separation is achieved on a C18 Chromolith column (Chromolith Performance, 100 x 4.6 mm ID), using as mobile phase water/acetonitrile/methanol (72:18:10 vol/vol/vol) mixed with 0.1% of 85% phosphoric acid. Isocratic elution is conducted at a flow-rate of 1.5 mL min-1. Total duration of a chromatographic run is 7 min. Calibration curves are linear over the 25-2000 ng mL-1 concentration range, with a limit of quantitation of 25 ng mL-1. Other performance characteristics include high precision (intra- and inter-day coefficients of variation ≤ 12.6%) and high accuracy (99.7 to 108.7%). The method is suitable for the investigation of concentration-response relationships in patients receiving therapeutic doses of retigabine.
      PubDate: 2017-12-12T23:32:03.209398-05:
      DOI: 10.1002/bmc.4168
  • Development of HPLC with fluorescent detection using NBD-F for the
           quantification of colistin sulfate in rat plasma and its pharmacokinetic
    • Authors: Sui Ouchi; Kazuaki Matsumoto, Maki Okubo, Yuta Yokoyama, Junko Kizu
      Abstract: Colistin sulfate, composed of a mixture of colistin A sulfate (CLA) and colistin B sulfate (CLB), is available for treating life-threatening infections caused by multidrug-resistant Gram-negative bacteria. In this study, the CLA and CLB were quantified separately. Colistin sulfate was extracted from rat plasma with a solid-phase extraction C18 cartridge and reacted with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), and the fluorescent derivatives were subjected to reversed phase high-performance liquid chromatography analysis and used to investigate the pharmacokinetics of CLA and CLB in rat plasma.The recovery rates of CLA and CLB were 41.2 ± 4.4% and 45.5 ± 3.1%, respectively. The recovery rate calculated from the total area of CLA and CLB was 43.9 ± 3.6%. When 2 mM NBD-F and 10 mM boric acid buffer (pH 9.5) were added to colistin sulfate, the highest recovery rate was obtained. The best heating time was 5 min at 60°C. The lower limits of quantification for CLA, CLB, and the total area of CLA and CLB were 0.05, 0.05 and 0.1 μg/mL; the coefficients of variations were 13.5%, 14.5% and 14.1%, respectively. This method was found to have acceptable linearity, precision, and accuracy, and has been successfully applied to a pharmacokinetic study in rat plasma.
      PubDate: 2017-12-12T22:31:14.846353-05:
      DOI: 10.1002/bmc.4167
  • The determination of polycyclic aromatic hydrocarbons (PAHs) in human
           urine by high-resolution gas chromatography-mass spectrometry
    • Authors: Sung-Hee Cho; Sun-Kyung Lee, Chong Hyeak Kim
      Abstract: Polycyclic aromatic hydrocarbons (PAHs), the organic compounds formed by at least two condensed aromatic rings, are ubiquitous environmental pollutants that are produced by incomplete combustion of organic materials. PAHs have been classified as carcinogen to humans by the International Agency for Research on Cancer (IARC), because they can bind to DNA, causing mutations. Therefore, the levels of PAHs in human urine can be used as an indicator for potential carcinogenesis and cell mutation. The analytical method was developed for the accurate measurement of PAHs in urine using high-resolution gas chromatography-mass spectrometry. Urine samples were extracted by an Oasis HLB extraction cartridge after enzymatic hydrolysis with β-glucuronidase/arylsulfatase cocktail. The 18 PAHs were separated using Agilent DB-5 MS capillary column (30 m × 0.25 mm, 0.25 μm) and monitored by time of flight mass spectrometry. Under the optimized method, the linearity of calibration curves was higher than 0.994. The limits of detection (LOD) at signal to noise (S/N) ratio of 3 were 10–100 ng/L. The coefficients of variation were in the range of 0.4–9.0%. The present method was highly accurate for simultaneous determination of 18 PAHs in human urine and could be applied to monitoring and biomedical investigations to check exposure of PAHs.
      PubDate: 2017-12-12T22:11:40.22457-05:0
      DOI: 10.1002/bmc.4166
  • Simultaneous determination of isochamaejasmin, neochamaejasmin A, and
           aphnoretinin rat plasma by UPLC–MS/MS and its application to a
           pharmacokinetic study of Stellera chamaejasme L. extract
    • Authors: Ludi Wang; Wei Yang, Siyang Wu, Shuyao Wang, Chen Kang, Xiaoli Ma, Yingfei Li, Chuan Li
      Abstract: Isochamaejasmin, neochamaejasmin A, and daphnoretin derived from Stellera chamaejasme L. are important because of their reported anti-cancer properties. In this study, a sensitive UPLC–MS/MS method for the determination of isochamaejasmin, neochamaejasmin A, and daphnoretin in rat plasma was developed. The analyte and IS were separated on an Acquity UPLC HSS T3 column (100 × 2.1 mm, 1.8μm) using gradient elution with the mobile phase of aqueous solution (methanol/water, 1:99, v/v, containing 1 mM formic acid) and organic solution (methanol/water, 99:1, v/v, containing 1 mM formic acid) at a flow rate of 0.3 mL/min. Multiple reaction monitoring mode with negative electrospray ionization interface was carried out to detect the components. The method was validated in terms of specificity, linearity, accuracy, precision, stability, etc.. Excellent linear behavior was observed over the certain concentration ranges with the correlation coefficient values higher than 0.99.Intra- and inter-day precisions (RSD, %) were less than 6.7% and accuracy (RE, %) ranged from −7.0 to 12.0%. The validated method was firstly and successfully applied to investigate the pharmacokinetics of three chemical ingredients after oral administration of Stellera chamaejasme L. extract to rats.
      PubDate: 2017-12-12T21:48:02.086043-05:
      DOI: 10.1002/bmc.4162
  • Simultaneous determination of etonogestrel and ethinyl estradiol in human
           plasma by UPLC-MS/MS and its pharmacokinetic study
    • Authors: Sneha G. Nair; Daxesh P. Patel, Frank J. Gonzalez, Bhargav M. Patel, Puran Singhal, Darshan V. Chaudhary
      Abstract: A selective, sensitive and rapid ultra-performance liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of etonogestrel (ENG) and ethinyl estradiol (EE) in human plasma. The analytes and their deuterated internal standard, ENG-d7 and EE-d4 were extracted from plasma samples by solid phase extraction on HyperSep™ Retain PEP Cartridges. The chromatographic analysis was performed on ACQUITY UPLC HSS Cyano column, 100 A° (50 mm × 2.1 mm, 1.8 μm) column using gradient mobile phase, acetonitrile and 2.0 mM ammonium trifluoroacetate (ATFA) at 0 to 1.7 min (65:35, v/v) and 1.8 to 2.7 min (95:5, v/v) with 0.250 mL/min flow rate. Analytes and IS, protonated precursor product ion transitions (ENG: m/z 325.2257.2, EE: m/z 530.2171.2, ENG-d7: m/z 332.2263.2, EE-d4: m/z 534.2171.2) were monitored on a TQMS, operating in MRM and positive ionization mode. The calibration curves were established at 10.00-2500 pg/mL for ENG and 1.500-150.0 pg/mL for EE with a correlation coefficient (r2) ≥ 0.9996 for both. The validated method was successfully applied to support a bioequivalence study of 0.15 mg ENG and EE 0.03 mg tablet formulation, administered in 24 healthy Indian females. Method reliability was assessed by reanalysis of 94 incurred study samples.
      PubDate: 2017-12-11T14:40:40.582578-05:
      DOI: 10.1002/bmc.4165
  • Characterization of Forsythoside A Metabolites in Rats by a Combination of
           UHPLC-LTQ-Orbitrap Mass Spectrometer with Multiple Data Processing
    • Authors: Fei Wang; Guang-shang Cao, Yun Li, Lu-lu Xu, Zhi-bin Wang, Ying Liu, Jian-qiu Lu, Jia-yu Zhang
      Abstract: Forsythoside A (FTA), the main active constituent isolated from Fructus Forsythiae, has various biological functions including anti-oxidant, anti-viral and anti-microbial activities. However, while researches on FTA have been mainly focused on the treatment of diseases on material basis, FTA metabolites in vivo have not been comprehensively evaluated. Here, a rapid and sensitive method using UHPLC-LTQ-Orbitrap mass spectrometer with multiple data processing techniques including high-resolution extracted ion chromatograms (HREICs), multiple mass defect filters (MMDFs) and diagnostic product ions (DPIs) was developed for screening and identification of FTA metabolites in rats. As the result, a total of 43 metabolites were identified in biological samples including 42 metabolites in urine, 22 metabolites in plasma and 15metabolites in feces. These results demonstrated that FTA underwent a series of in vivo metabolic reactions including methylation, dimethylation, sulfation, glucuronidation, diglucuronidation, cysteine conjugation and their composite reactions. The research enhanced our understanding of FTA metabolism and built the foundation for its further toxicity and safety studies.
      PubDate: 2017-12-11T13:40:31.889345-05:
      DOI: 10.1002/bmc.4164
  • A fast and accurate isotope dilution GC-IT-MS/MS method for determination
           of eugenol in different tissues of fish: application to a depletion study
           in mandarin fish
    • Authors: Yongtao Liu; Xiaohui Ai, Le Li, Jincheng Li, Hong Yang
      Abstract: An accurate, rapid and effective method was established for determination of eugenol in plasma, muscle, skin, liver, kidney and gill of fish using gas chromatography-ion trap tandem mass spectrometry (GC-IT-MS/MS). Samples of muscle, skin, liver, kidney and gill were prepared using the modified QuEChERS (quick, easy, cheap, effective, rugged and safe) procedure, and plasma sample was prepared by a liquid-liquid extraction procedure. Eugenol was monitored in less than 7 min using an electron-ionization source (EI) in MS/MS mode and quantified by internal standard (IS) of eugenol-d3. The limit of detection (LOD) was 5.0 μg/kg, and the limit of quantification (LOQ) was 10.0 μg/kg. The calibration curve was linear in the range of 5–1000 μg/L (R2 = 0.9996). Intra- and inter- precisions of eugenol expressed as an RSD within 9.74%, and the accuracy exhibited an RE ranged from -2.20% and 8.89%. The developed method was successfully used to study the elimination regularity of eugenol in mandarin fish.
      PubDate: 2017-12-11T08:45:52.807079-05:
      DOI: 10.1002/bmc.4163
  • Simultaneous determination of residues of metalaxyl, cyazofamid, and a
           cyazofamid metabolite in tobacco leaves and soil by liquid chromatography
           with tandem mass spectrometry
    • Authors: Sizhuo Wu; Weiwei Yu, Caiyuan Sun, Kunming Zheng, Haizhen Zhang, Min Huang, Deyu Hu, Kankan Zhang
      Abstract: A simple method was developed and validated for the simultaneous determination of metalaxyl, cyazofamid, and the cyazofamid metabolite 4-chloro-5-p-tolylimidazole-2-carbonitrile (CCIM) by liquid chromatography with tandem mass spectrometry. The three target compounds were extracted from tobacco and soil with acetonitrile containing 0.1% acetic acid, and the extracts were purified using octadecylsilane. The proposed method showed satisfactory linearity (R2 ≥ 0.9985) for the target compounds. The limits of detection for metalaxyl, cyazofamid, and CCIM were 0.006, 0.06 and 0.06 mg/kg in soil and green tobacco leaves and 0.03, 0.3, and 0.3 mg/kg in cured tobacco leaves, respectively. The limits of quantification for metalaxyl, cyazofamid, and CCIM were 0.02, 0.2 and 0.2 mg/kg in soil and green tobacco leaves and 0.1, 1, and 1 mg/kg in cured tobacco leaves, respectively. The average recoveries from soil and tobacco were 72.91%–98.40% for metalaxyl, 76.73%–105.80% for cyazofamid, and 74.48%–106.45% for CCIM. The relative standard deviation range was 1.23%–6.99%. The developed method was successfully applied to analysis of residues of metalaxyl, cyazofamid, and CCIM in real soil and tobacco samples. The results indicated that the established method could meet the requirement for the analysis of trace amounts of all three analytes in soil and tobacco.
      PubDate: 2017-12-11T05:22:54.124176-05:
      DOI: 10.1002/bmc.4161
  • Biotransformation and metabolic profile of Xian-Ling-Gu-Bao capsule, a
           traditional Chinese medicine prescription, with rat intestinal microflora
           by ultra performance liquid chromatography coupled with quadrupole
           time-of-flight tandem mass spectrometry analysis
    • Authors: Meng-xue Gao; Xi-yang Tang, Feng-xiang Zhang, Zhi-hong Yao, Xin-sheng Yao, Yi Dai
      Abstract: Xian-Ling-Gu-Bao capsule (XLGB), a well-known traditional Chinese medicine prescription (TCMP), has been used for prevention and treatment of osteoporosis. The safety and efficacy of XLGB have been confirmed based on the principle of evidence-based medicine (EBM). XLGB is usually administered orally, after which its multi-components are brought into contacted with intestinal microflora in the alimentary tract and biotransformed. However, investigations on the comprehensive metabolic profile of XLGB are absent. In this study, twelve representative compounds bearing different typical structures (including iridoid glycosides, prenylated flavonol glycosides, prenylated flavonoids, triterpenoid saponins, steroidal saponins, coumarins and monoterpene phenols) were selected and then investigated for their biotransformation in rat intestinal microflora. In addition, metabolic profile of XLGB in rat intestinal microflora was investigated by ultra performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS). As a result, a total of 87 biotransformation components were identified from incubated solution of twelve representative compounds and XLGB, which underwent sixteen metabolic reactions (including deglycosylation, glycosylation, dehydrogenation, hydrogenation, oxidation, epoxidation, hydroxylation, dehydration, hydration, hydrolysis, methylation, isomerization, cyclization, pyrolysis reaction, amino acid conjugation and nucleophilic addition reaction with NH3). It demonstrated that deglycosylation reaction by cleavage of the sugar moieties was the main metabolic pathway of a variety of glycosides, including prenylated flavonol glycosides, coumarin glycosides, iridoid glycosides and saponins. In addition, compared with the biotransformation of twelve representative compounds, different biotransformed fate was observed in the XLGB incubated samples of rat intestinal microflora. It is worth noting that the amino acid conjugation was firstly discovered in metabolism of prenylated flavonol glycosides in rat intestinal microflora.
      PubDate: 2017-12-11T04:50:07.25475-05:0
      DOI: 10.1002/bmc.4160
  • Liquid chromatographic methods for the therapeutic drug monitoring of
           methotrexate as clinical decision support for personalized medicine: a
           brief review.
    • Authors: Mónica Francisco Silva; Cláudia Ribeiro, Virgínia M.F. Gonçalves, Maria Elizabeth Tiritan, Áurea Lima
      Abstract: Methotrexate (MTX) is an antifolate drug used for several diseases. Depending on the disease, MTX can be administered at low-dose (LDMTX) in some autoimmune diseases, like rheumatoid arthritis, or at high-dose (HDMTX) in some cancers, such as acute lymphoblastic leukaemia. After absorption, MTX is metabolized in the liver to 7-hydroxymethotrexate (7-OH-MTX) and in the intestine to 2,4-diamino-N10-methylpteroic acid (DAMPA). Moreover, inside red blood cells (RBCs), MTX is converted to active metabolites, MTX polyglutamates (MTXPGs), contributing to its pharmacodynamics. Due to its narrow therapeutic range, and inter and intra-patient variability, either non-effectiveness and/or toxicity may occur. Because of the existence of a relationship between drug therapeutic outcome and its systemic concentration, therapeutic drug monitoring (TDM) may ensure effectiveness and safety of MTX use. In order to monitor the optimization of patient clinical response profile, several analytical methods have been described for the TDM in biological samples. These include liquid chromatography (LC) coupled with ultraviolet detection (UV), fluorescence detection (FD) or mass spectrometry (MS), each one presenting advantages and drawbacks. This paper reviews the most commonly used techniques for sample preparation and critically discusses the current LC methods applied for the TDM of MTX in biological samples, at LDMTX and HDMTX.
      PubDate: 2017-12-11T03:11:12.262231-05:
      DOI: 10.1002/bmc.4159
    • Authors: Mehmet Gumustas; Mehmet Gokhan Caglayan, Feyyaz Onur, Sibel A. Ozkan
      Abstract: A combination of antiretroviral agents is frequently used in effective treatment of the Human Immunodeficiency Virus infection. In this study, two different separation methods are presented for the simultaneous determination of emtricitabine, rilpivirine, and tenofovir from raw materials and urine samples. Developed liquid chromatography and capillary electrophoresis methods were thoroughly optimized for high analytical performances. Optimization of multiple variables at the same time by performing a minimum number of experiments was achieved by the Box-Behnken design, which is an experimental design in Response Surface Methodology, in capillary electrophoresis. The results of the experimental design ensure minimum analysis time with well separated analytes. Separation conditions, such as different stationary phases, pH level, organic modifiers, and temperatures in liquid chromatographic method, were also optimized. Especially, among stationary phases, core-shell column especially enhanced the effectiveness of separation in liquid chromatography. Both methods were fully validated and applied to real samples. The main advantage of the developed methods is the separation of the drug combination in a short time with high efficiency and without any time-consuming steps.
      PubDate: 2017-12-07T19:40:23.561486-05:
      DOI: 10.1002/bmc.4158
  • Development and validation of an LC-MS/MS method for the determination of
           a novel thienoquinolin urea transporter inhibitor PU-48 in rat plasma and
           its application to a pharmacokinetic study
    • Authors: Zhi-Yuan Zhang; Xin Wang, Dan Liu, Hua Zhang, Qiang Zhang, Ying-Yuan Lu, Pu Li, Ya-Qing Lou, Bao-Xue Yang, Chuang Lu, Ya-Xin Lou, Guo-Liang Zhang
      Abstract: A specific, sensitive and stable high-performance liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative determination of methyl 3-amino-6-methoxythieno [2,3-b]quinoline-2-carboxylate (PU-48), a novel diuretic thienoquinolin urea transporter inhibitor in rat plasma. In this method, the chromatographic separation of PU-48 was achieved with a reversed phase C18 column (100 × 2.1 mm, 3 μm) at 35 °C. The mobile phase consisted of acetonitrile and water with 0.05 % formic acid added with a gradient elution at flow rate of 0.3 mL/min. Samples were detected with the triple-quadrupole tandem mass spectrometer with multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source in positive mode. The retention time were 6.2 min for PU-48 and 7.2 min for megestrol acetate (internal standard, IS). The monitored ion transitions were mass-to-charge ratio (m/z) 289.1 229.2 for PU-48 and m/z 385.3267.1 for the internal standard. The calibration curve for PU-48 was linear over the concentration range of 0.1–1000 ng/mL (r2> 0.99), and the lower limit of quantitation (LLOQ) was 0.1 ng/mL. The precision, accuracy and stability of the method were validated adequately. The developed and validated method was successfully applied to the pharmacokinetic study of PU-48 in rats.
      PubDate: 2017-11-28T18:07:04.299931-05:
      DOI: 10.1002/bmc.4157
  • Simultaneous determination of tryptophan, kynurenine, kynurenic acid,
           xanthurenic acid and 5-hydroxytryptamine in human plasma by LC-MS/MS and
           its application to acute myocardial infarction monitoring
    • Authors: Qing Tong; Jia Song, Guangjie Yang, Li Fan, Wei Xiong, Jianguo Fang
      Abstract: The reliable methods for the determination of tryptophan and its metabolites are vital to the monitoring of biochemical state during the initiation and progression of cardiovascular disease. In the present study, a single-run liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of tryptophan (Trp) and its metabolites including kynurenine (Kyn), kynurenic acid (KA), xanthurenic acid (XA) and 5-hydroxytryptamine (5-HT) in human plasma. The plasma samples were prepared using a protein precipitation approach, and the chromatographic separation was performed by gradient elution on a C18 column within a total analysis time of 3.5 min. The calibration ranges were 40-20000 ng/mL for Trp, 4-2000 ng/mL for Kyn, 0.2-100 ng/mL for KA, 0.4-200 ng/mL for XA and 1-500 ng/mL for 5-HT, and the precision and accuracy were acceptable. The evaluation of recovery and IS-normalized matrix effect proved that the sample preparation approach was effective and the matrix effect could be negligible. The newly developed method was successfully applied to the analysis of plasma samples from healthy individuals and myocardial infarction patients. The findings suggested that the plasma concentrations of Trp, Kyn, 5-HT as well as the concentration ratios of Kyn/Trp and Trp/5-HT might serve as biomarkers for the monitoring of acute myocardial infarction.
      PubDate: 2017-11-28T02:26:57.101356-05:
      DOI: 10.1002/bmc.4156
  • Pharmacokinetics and Tissue Distribution of pefloxacin mesylate in
    • Authors: Shuqian Lin; Guiming Li, Zengcheng Zhao, Jian Fu, Minyan Feng, Minxun Song, Zhongli Huang, Shifa Yang, Shuli Wang, Renzhong Wan
      Abstract: A specific, sensitive and stable high-performance liquid chromatography (HPLC)-based analytical method was established to determine the level of pefloxacin mesylate (PM) in the plasma and various tissues of chickens. Chickens were randomly assigned to 12 equal experiment groups, including 11 treatment groups and one control group. The chickens in the treatment groups received oral administration of PM and were sacrificed at different pre-determined time points, with their blood and various organs harvested, extracted and analyzed by HPLC to quantify the level of the residual antibiotic. Method validation studies indicated that the HPLC measurement showed excellent precision, reproducibility, stability and robustness. The obtained pharmacokinetic parameters suggested that PM reached peak levels in various tissues within 1-2 h after its oral administration, and was mainly concentrated in liver and kidney. The antibiotic was also found to be cleared from chicken crureus, brain, testes, ovaries and pancreas at higher rates compared to other organs. Overall, the rapid accumulation of PM could at least be partially attributed to its relatively slow organ clearance. These results could serve as a useful guidance for the rational use of PM and other quinolone-derived antimicrobials in the treatment of infectious diseases in chickens and other animals.
      PubDate: 2017-11-27T03:30:24.809764-05:
      DOI: 10.1002/bmc.4154
  • Stress Degradation of Edaravone: Separation, Isolation and
           Characterization of Major Degradation Products
    • Authors: Madhuri Baghel; Sadhana J. Rajput
      Abstract: In the present study ICH prescribed stress degradation was carried out to study the degradation profile of Edaravone. For establishing QbD assisted stability indicating assay, the reaction solutions in which different degradation products were formed were mixed. Plackett burman and central composite design was used to screen and optimize experimental variables to resolve Edaravone and its impurities with good peak symmetry using a RP C-18 column. The method was validated according to ICH guidelines. Seven unknown and two known degradation products were identified and characterized by LC-MS/MS. Two major degradation products formed under thermal degradation were isolated and characterized as 4-(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl-4-(4,5-dihydro-5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one and 3-hydroxy-dihydro-thiazolo(1-(2-methyl-buta-1,3dienyl)-1-phenylhydrazine)5-one. The degradation pathways of degradants were proposed based on m/z values.
      PubDate: 2017-11-23T23:50:47.132999-05:
      DOI: 10.1002/bmc.4146
  • Dissipation, residues and risk assessment of spirotetramat and its four
           metabolites in citrus and soil under field conditions by LC-MS/MS
    • Authors: Qingtao Zhang; Yuling Chen, Shouyi Wang, Yurong Yu, Ping Lu, Deyu Hu, Zaihui Yang
      Abstract: A modified Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) method for the simultaneous determination of spirotetramat and its four metabolite residues in citrus, peel, pulp and soil was developed and validated by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The samples were extracted with acetonitrile (1%, glacial acetic acid, v/v) and purified using primary secondary amine and octadecylsilane. The limit of detection was 0.01–0.13 mg/kg, whereas that of quantification was 0.02–0.40 mg/kg for spirotetramat and its metabolites. The average recoveries of spirotetramat, spirotetramat-enol, spirotetramat-mono-hydroxy, spirotetramat-enol-glucoside and spirotetramat-ketohydroxy in all matrices were 73.33–107.91%, 75.93–114.85%, 76.44–100.78%, 71.46–103.19% and 73.08–105.27%, respectively, with relative standard deviations < 12.32%. The dissipation dynamics of spirotetramat in citrus and soil followed first-order kinetics, with half-lives of 2.3–8.5 days in the three sampling locations. The terminal residues of spirotetramat in four matrices at the three locations measured below the 1.0 mg/kg maximum residue limit set by China, and residues were found to be concentrated on the peel. The risk assessment of citrus was evaluated using risk quotients (RQs). The RQ values were found to be significantly lower than 1, suggesting that the risk to human health was negligible when using the recommended doses of spirotetramat in citrus. These results could provide guidance for the safe and proper application of spirotetramat in citrus in China.
      PubDate: 2017-11-23T19:25:24.718904-05:
      DOI: 10.1002/bmc.4153
  • Simultaneous determination of kaempferol, quercetin, mangiferin, gallic
           acid, p-hydroxybenzoic acid, and chlorpheniramine maleate in rat plasma
           after oral administration of Mang-Guo-Zhi-Ke Tablets by UHPLC-MS/MS and
           its application to pharmacokinetics
    • Authors: Weijie Xu; Jiagang Deng, Yiyun Qian, Xiao-tao Hou, Zhenhua Zhu, Ming Zhao, Erxin Shang, Dawei Qian, Huiting Zeng, Hanqing Pang, Jinao Duan
      Abstract: Mang-Guo-Zhi-Ke Tablets (MGZKTS) is an effective Chinese patent medicine, contains mango leaf extract as the main raw material, and the antihistamine drug, chlorpheniramine maleate, is included in the formulation. However, its pharmacokinetic effect is rarely reported. A highly sensitive, reliable and rapid high-throughput method using ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was used to simultaneously determine kaempferol, quercetin, mangiferin, p-hydroxybenzoic acid, gallic acid and chlorpheniramine maleate in rat plasma after oral administration of MGZKTS. The method was successfully developed and fully validated to investigate the pharmacokinetics of MGZKTS. Chloramphenicol and clarithromycin were used as internal standards (IS). A practicable protein precipitation procedure with methanol was adopted for sample preparation. The samples were separated on an Acquity UHPLC Syncronis C18 column (100 mm×2.1 mm, 1.7 μm) using 0.1% formic acid-acetonitrile as the mobile phase. The flow rate was set at 0.4 mL/min. The obtained calibration curves were linear in the concentration range of approximately 1-1000 ng/mL for plasma (r>0.99). Method validation results met the criteria reported in the United States Food and Drug Administration guidelines. Quercetin, p-hydroxybenzoic acid and kaempferol were absorbed rapidly and reached the Cmax between 0.16 h and 0.25 h. This validated that the UHPLC-MS/MS method was successfully applied to study the pharmacokinetic parameters of the six compounds in rat plasma after oral administration of MGZKTS. This evidence will be useful for the clinical rational use of Mang-Guo-Zhi-Ke tablets.
      PubDate: 2017-11-23T18:35:27.164455-05:
      DOI: 10.1002/bmc.4155
  • Comprehensive analysis of nine monoamines and metabolites in small amounts
           of peripheral murine (C57Bl/6J) tissues
    • Authors: Joachim Nagler; Sonja C. Schriever, Meri De Angelis, Paul T. Pfluger, Karl-Werner Schramm
      Abstract: Monoamines, acting as hormones and neurotransmitters, play a critical role in multiple physiological processes ranging from cognitive function and mood to sympathetic nervous system activity, fight-or-flight response, or glucose homeostasis. In addition to brain and blood, monoamines are abundant in several tissues, and dysfunction in their synthesis or signaling is associated with various pathological conditions. It was our goal to develop a method to detect these compounds in peripheral murine tissues.In this study, we employed a high performance liquid chromatography method using electrochemical detection that allows not only detecting the catecholamines but a detailed analysis of nine monoamines and metabolites in murine tissues. Simple tissue extraction procedures were optimized for muscle (gastrocnemius, extensor digitorum longus, and soleus), liver, pancreas, and white adipose tissue in the range of weight between 10¬200 mg.The system allowed a limit of detection between 0.625 pg μL-1 and 2.5 pg μL-1 for monoamine analytes and their metabolites, including dopamine, 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine, homovanillic acid, norepinephrine, epinephrine, 3-methoxy-4-hydroxyphenylglycol, serotonin, and 5-hydroxyindoleacetic acid. Typical concentrations for different monoamines and their metabolization products in these tissues are presented for C57Bl/6J mice fed a high fat diet.
      PubDate: 2017-11-22T18:30:31.409376-05:
      DOI: 10.1002/bmc.4151
  • Statistical optimization of an RP-HPLC method for the determination of
           selected flavonoids in berry juices and evaluation of their antioxidant
    • Authors: Andrija Ciric; Milena Jelikic-Stankov, Milica Cvijovic, Predrag Djurdjevic
      Abstract: An isocratic RP-HPLC method for the separation and identification of selected flavonoids (quercetin, rutin, luteolin-7-O-glucoside, kaempferol, and kaempferol-3-O-glucoside) in commercial berries juices (blackcurrant, blueberry, red raspberry and cherry) was developed with the aid of central composite design and response surface methodology.The optimal separation conditions were a mobile phase of 85:15 (% v/v) water/acetonitrile, pH of 2.8 (adjusted with formic acid), flow rate 0.5 mL/min and column temperature of 35 °C.The obtained levels of bioflavonoids (mg/100 mL of juice) were as follows: for quercetin, ca. 0.21 - 5.12; for kaempferol, ca. 0.05 - 1.2; for rutin, ca. 0.4 - 6.5; for luteolin-7-O-glucoside, ca. 5.6 - 10.2; and for kaempferol-3-O-glucoside, ca. 0.02 - 0.12. This is considerably lower than what is found in fresh fruits.Total phenolic, flavonoid and anthocyanin contents were determined spectrophotometrically. Total flavonoid content varied as follows: blackcurrant> blueberry> red raspberry> cherry.The antioxidant activity of juice extracts (DPPH and ABTS methods) expressed as IC50 values varied from 8.56 to 14.05 mg L-1. These values are approximately 2.5 to 3 times lower than quercetin, ascorbic acid and Trolox®, but compared to rutin and butylhydroxytoluene, berries show similar or better antioxidant activity by both the DPPH and ABTS methods.
      PubDate: 2017-11-22T13:25:19.906283-05:
      DOI: 10.1002/bmc.4150
  • Identification of Cytochrome P450 (CYP) isoforms involved in the
           metabolism of artocarpin and assessment of its drug-drug interaction (DDI)
    • Authors: Wei Qu; Xuezheng Liu
      Abstract: Artocarpin isolated from an agricultural plant Artocarpus communis has shows anti-inflammation and anticancer activities. In this study, we utilized recombinant human UDP-glucuronosyltransferasesupersomes (UGTs) and human liver microsomes (HLMs) to explore its inhibitory effect on UGTs and cytochrome p450 enzymes(CYPs). Chemical inhibition studies and screening assays with recombinant human CYPs were used to identify if CYP isoform is involved in artocarpin metabolism. Artocarpin showed strong inhibition against UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B7, CYP2C8 and CYP3A4. Especially, artocarpin exhibited competitive inhibition against CYP3A4 and noncompetitive inhibition against UGT1A3 and UGT1A7, respectively. The half inhibition concentration (IC50) values for CYP3A4, UGT1A3 and UGT1A7 were 4.67, 3.82 and 4.82 μM, and the inhibition kinetic parameters (Ki) for them were 0.78, 2.67 and 3.14 μM, respectively. After artocarpin was incubated in human liver microsomes and determined by HPLC, we observed its main metabolites (M1 and M2). In addition, we proved that CYP2D6 played the key role in the biotransformation of artocarpin in human liver microsomes. The result of molecular docking further confirmed artocarpin interacted with CYP2D6, CYP2C8 and CYP3A4 through hydrogen bonds, respectively. This study provided preliminary results for further research on artocarpin or artocarpin-containing herbs.
      PubDate: 2017-11-22T12:25:21.360679-05:
      DOI: 10.1002/bmc.4149
  • Simultaneous determination and method validation of clethodim and its
           metabolites clethodim sulfoxide and clethodim sulfone in tobacco by
    • Authors: Fei Wang; Guoqiang Yang, Jin Xu, Weiwei Yu, Lihong Shi, Song Zeng, Lingzhu Chen, Deyu Hu, Kankan Zhang
      Abstract: A simple method was developed and validated for the simultaneous determination of clethodim, clethodim sulfoxide, and clethodim sulfone in soil and tobacco by liquid chromatography with tandem mass spectrometry. The three target compounds were extracted from tobacco and soil with acetonitrile, and the extracts were purified using octadecyl silane. The proposed method showed satisfactory linearity (R2 ≥ 0.9973) for the target compounds. The limits of detection and quantitation of the three analytes in all matrices were 0.024−0.06 mg/kg and 0.08−0.2 mg/kg, respectively. The recovery was tested in blank soil and tobacco leaf samples and calculated to be 74.8%−104.4% with relative standard deviations of 1.9%−12.1%. The developed method was successfully applied to the analysis of residues of clethodim, clethodim sulfoxide, and clethodim sulfone in real soil and tobacco samples. The results indicated that the developed method can meet the requirements for the analysis of trace amounts of all three analytes in soil and tobacco.
      PubDate: 2017-11-22T11:06:21.145584-05:
      DOI: 10.1002/bmc.4148
  • Development and validation of a liquid chromatography-tandem mass
           spectrometry analytical method for the therapeutic drug monitoring of
           eight novel anticancer drugs
    • Authors: M. Herbrink; N. Vries, H. Rosing, A.D.R. Huitema, B. Nuijen, J.H.M. Schellens, J.H. Beijnen
      Abstract: To support therapeutic drug monitoring (TDM) of patients with cancer, a fast and accurate method for simultaneous quantification of the registered anticancer drugs afatinib, axitinib, ceritinib, crizotinib, dabrafenib, enzalutamide, regorafenib and trametinib in human plasma using liquid chromatography tandem mass spectrometry was developed and validated.Human plasma samples were collected from treated patients and stored at -20 oC. Analytes and internal standards (stable isotopically labeled analytes) were extracted with acetonitrile. An equal amount of 10 mM NH4CO3 was added to the supernatant to yield the final extract. Two μL of this extract was injected onto a C18-column, gradient elution was applied, and triple-quadrupole mass spectrometry in positive-ion mode was used for detection.All results were within the acceptance criteria of the latest US FDA guidance and EMA guidelines on method validation, except for the carry-over of ceritinib and crizotinib. These are corrected for by the injection order of samples. Additional stability tests were carried out for axitinib and dabrafenib in relation to their reported photostability.In conclusion, the described method to simultaneously quantify the eight selected anticancer drugs in human plasma was successfully validated and applied for therapeutic drug monitoring in cancer patients treated with these drugs.
      PubDate: 2017-11-22T10:25:20.47657-05:0
      DOI: 10.1002/bmc.4147
  • Development and validation of a simple solid-phase extraction method
           coupled with liquid chromatography–triple quadrupole tandem mass
           spectrometry for simultaneous determination of lincomycin, tylosin A, and
           tylosin B in royal jelly
    • Authors: Weijia Zheng; Jin-A Park, A.M. Abd El-Aty, Seong-Kwan Kim, Sang-Hyun Cho, Jeong-Min Choi, Mohamad Warda, Jing Wang, Jae-Han Shim, Ho-Chul Shin
      Abstract: We develop an analytical method for the determination of lincomycin, tylosin A, and tylosin B residues in royal jelly using liquid chromatography–triple quadrupole tandem mass spectrometry analysis. For extraction and purification, we employ 1% trifluoroacetic acid and 0.1 M Na2EDTA solutions along with an Oasis HLB cartridge. The target antibiotics were well separated in a Kinetex EVO C18 reversed-phase analytical column using a combination of 0.1% formate acid in ultrapure water (A) and acetonitrile (B) as the mobile phase. Good linearity was achieved over the tested concentration range (5–50 μg/kg) in matrix-matched standard calibration. The coefficients of determination (R2) were 0.9933, 0.9933, and 0.996, for tylosin A, tylosin B, and lincomycin, respectively. Fortified royal jelly spiked with 3 different concentrations of the tested antibiotics; 5, 10, and 20 μg/kg, yielded recoveries in the range 80.94–109.26% with relative standard deviations ≤ 4%. The proposed method was applied to monitor 11 brand of royal jelly collected from domestic markets and an imported brand from New Zealand; all the samples tested negative for lincomycin, tylosin A, and tylosin B residues. In conclusion, 1% trifluoroacetic acid and 0.1 M Na2EDTA aqueous solvents combined with solid-phase extraction could effectively complete the sample preparation process for royal jelly before analysis. The developed approach can be applied for a routine analysis of lincomycin, tylosin A, and tylosin B residues in royal jelly.
      PubDate: 2017-11-22T00:50:26.440891-05:
      DOI: 10.1002/bmc.4145
  • Effects of Tao-Hong-Si-Wu decoction on acute blood stasis in rats based on
           a LC-Q/TOF-MS metabolomics and network approach
    • Authors: Qi Ma; Peng-Ling Li, Yong-Li Hua, Peng Ji, Wan-Ling Yao, Xiao-Song Zhang, Li-Jia Zhong, Yan-Ming Wei
      Abstract: A novel approach using metabolomics coupled with a metabolic network was used to investigate the effects of THSWD on the rat model of acute blood stasis syndrome. Acute blood stasis syndrome was induced by placing the rats in ice-cold water following two injections with epinephrine. The hemorheological indicators (WBV and PV), and the blood coagulation indicators (TT, PT, APTT, and FIB) were detected. The nonparametric univariate method and multivariate statistical analysis were performed for determining the potential biomarkers. A correlation map was structured between biochemical indicators and hub metabolites to explain the effects mechanism of THSWD. After the administration of THSWD, the levels of WBV, PV, TT, APTT, and FIB returned to levels observed in the control group. According to metabolomics coupled with metabolic network analysis, the intervention of THSWD in rats with acute blood stasis syndrome induced substantial and characteristic changes in their metabolic profiles. Fifteen metabolites were screened, which mainly involved ten pathways and five hub metabolites, namely, L-glutamate, L-phenylalanine, N-acylsphingosine, arachidonic acid and phosphatidate. The biochemical indicators and hub metabolites could be adjusted close to normal levels by THSWD. Therefore, combining metabolomics and metabolic network helped evaluate the effects of THSWD on acute blood stasis.
      PubDate: 2017-11-17T09:02:07.472293-05:
      DOI: 10.1002/bmc.4144
  • Determination of Cefoperazone and Sulbactam in serum by HPLC-MS/MS: an
           adapted method for therapeutic drug monitoring in children
    • Authors: Xiu-Jun Wu; Xin Huang, Hai-Yan Shi, Xing-Kai Chen, Qian Dong, Guo-Xiang Hao, Yan Li, Yi Zheng, Wei Zhao
      Abstract: A rapid, accurate and specific high-performance liquid chromatographic -tandem mass spectrometry method has been validated for the simultaneous determination of cefoperazone and sulbactam in a small volume sample for children. A Shim-pack XR-ODS C18 column with gradient elution of water (0.1% formic acid) and acetonitrile (0.1% formic acid) solution was used for separation at a flow rate of 0.3 mL/min. The calibration curves of two analytes in serum showed excellent linearity over the concentration ranges of 0.03-10 μg/mL for cefoperazone, and 0.01-3 μg/mL for sulbactam, respectively. This method involves simple sample preparation steps and was validated according to standard FDA and EMA guidelines in terms of selectivity, linearity, detection limits, matrix effects, accuracy, precision, recovery, and stability. This assay can be easily implemented in clinical practice to determine concentrations of cefoperazone and sulbactam in children.
      PubDate: 2017-11-17T08:10:23.905671-05:
      DOI: 10.1002/bmc.4143
  • Comparative pharmacokinetics study of orientin in rat plasma by
           UHPLC-MS/MS after intravenous administration of single orientin and
           Trollius chinensis Bunge extract
    • Authors: Nan Zhao; Qi Sun, Yang Song, Lin Wang, Tingjian Zhang, Fanhao Meng
      Abstract: Orientin showed a broad array of biological activities, and it is the major bioactive compound in the Trollius chinensis Bunge. Thus, this paper was conducted to investigate the comparative pharmacokinetics of orientin after intravenous administration of single orientin and Trollius chinensis Bunge extract. Sample preparation involved a simple one-step deproteinization procedure with acetonitrile. Chromatographic separation was achieved on a Waters BEH C18 column with a mobile phase consisting of acetonitrile and water containing 0.1% formic acid in an isocratic elution way. The detection was accomplished by multiple reaction monitoring mode with the positive electrospray ionization. The pharmacokinetic properties of orientin were compared after the intravenous administrations of pure orientin and Trollius chinensis Bunge extract to rats with approximately the same dosage of 10mg/kg. Results of the study indicated that the pharmacokinetics of orientin in rat plasma have significant differences between two groups. It is workable on the clinical uses of therapeutic dosing of orientin and Trollius chinensis Bunge.
      PubDate: 2017-11-17T07:16:21.837782-05:
      DOI: 10.1002/bmc.4142
  • Metabolic study of paeoniflorin and total paeony glucosides from Paeoniae
           Radix Rubra in rats by high performance liquid chromatography coupled with
           sequential mass spectrometry (UPLC-ESI-MSn)
    • Authors: Lijun Zhu; Shanshan Sun, Yanxi Hu, Yufeng Liu
      Abstract: A clear understanding of the metabolism of Traditional Chinese Medicine (TCM) is extremely important in their rational clinical application and effective material foundation research. A novel and reliable strategy was performed to find more metabolites of paeoniflorin, determine the metabolites of total paeony glucosides (TPG) by means of determining those metabolites of paeoniflorin, and compare the metabolism differences between paeoniflorin and TPG by intragastric administration. This strategy was characterized as follows: firstly, the rats were divided into two groups (the paeoniflorin group and the TPG group) to find different metabolism mechanism between paeoniflorin and TPG; secondly, UPLC-FT-ICR MS and UPLC-Q-TOF MS2 were applied to obtain accurate molecular weight and structural information respectively; thirdly, the metabolites were tentatively identified by a combination of data-processing methods including mass defect screening, characteristic neutral loss screening and product ion screening; finally, a comparative study was employed in the metabolism of paeoniflorin and TPG. Based on the strategy, eighteen metabolites of paeoniflorin (including four new compounds) and eleven metabolites of TPG (including two new compounds) were identified respectively. In all of the identified metabolites of paeoniflorin, two metabolites in rat plasma, four metabolites in rat urine and six metabolites in rat feces were found for the first time after paeoniflorin administration, respectively. The results indicated that the hydrolyzation of the ester bond and glucosidic band and the conjugation with glucuronide were the major metabolic pathways of paeoniflorin. It has been the first time to detect the metabolites of paeoniflorin and TPG in rats plasma, urine and feces after intragastric administration. The results may contribute to a better understanding of the metabolism mechanism and providing a scientific rationale for researching the material basis of paeoniflorin and TPG in vivo.
      PubDate: 2017-11-17T06:15:46.257061-05:
      DOI: 10.1002/bmc.4141
  • Determination of Telbivudine in the Plasma of Chronic Hepatitis B Patients
           in Long-Term Treatment by High-Performance Liquid Chromatographic-Tandem
           Mass Spectrometry
    • Authors: Bicui Chen; Li Chen, Cai Cheng, Mingkang Zhong, Xiaojin Shi, Jiming Zhang, Bin Wang
      Abstract: Usually, creatine kinase elevation is commonly reported in telbivudine-treated patients. However, little is known abosut the relationship between this adverse drug reaction and plasma concentration. In this study, a sensitive, rapid and safe quantitative bioanalytical method has been established by using LC-MS/MS for the determination of telbivudine in a clinical study of chronic hepatitis B (CHB) patients. The assay was linear in a dynamic 10-10,000 ng/mL range (r2> 0.999) and total analysis time was 6 min in this method. The validated method was applied to quantitatively determine plasma concentration in CHB patients during long-term telbivudine treatment. The results revealed that telbivudine concentration in CK-elevated group (707.92- 2788.78 ng/mL) was significantly higher than those of normal CK (412.63- 1108.32 ng/mL). This method was adapted for therapeutic drug monitoring.
      PubDate: 2017-11-17T06:00:20.964149-05:
      DOI: 10.1002/bmc.4140
  • Development and validation of a high-performance liquid chromatography
           method for determination of lisinopril in human plasma by magnetic
           solid-phase extraction and pre-column derivatization
    • Authors: Noushin Rastkari; Reza Ahmadkhaniha
      Abstract: A sensitive, reliable and simple HPLC method was developed for the determination of lisinopril in human plasma. The method consists of extraction and clean-up steps based on magnetic solid-phase extraction and pre-column derivatization with a fluorescent reagent. The mobile phase consisted of a mixture of methanol–sodium dihydrogen phosphate (pH 3.0; 0.005 m; 75:25, v/v). The flow rate was set at 0.7 mL/min. Fluorescence detection was performed at 470nm excitation and 530nm emission wavelengths. Total chromatography run time was 5 min. The average extraction recovery of lisinopril and fluvoxamine (internal standard) was ≥82.8%. The limits of detection and quantification were determined as 1 and 3 ng/mL respectively. The method exhibited a linear calibration line over the concentration range of 3–1000 ng/mL with coefficient of determination (r2) of ≥0.98. The within-run and between-run precisions were satisfactory with values of CV of 1.8–12.8% (accuracy from 99.2 to 94.7%) and 2.4–13.7% (accuracy from 99.5 to 92.2%), respectively. These developments led to considerable improvement in method sensitivity and reliability. The method was validated according to the US Food and Drug Administration guidelines. Therefore, it can be considered as a suitable method for determination of lisinopril in plasma samples.
      PubDate: 2017-11-16T23:40:35.341228-05:
      DOI: 10.1002/bmc.4120
  • Simultaneous determination of tilianin and its metabolites in mice using
           ultra-high-performance liquid chromatography with tandem mass spectrometry
           and its application to a pharmacokinetic study
    • Authors: Liping Wang; Qingwei Chen, Lijun Zhu, Xuejun Zeng, Qiang Li, Ming Hu, Xinchun Wang, Zhongqiu Liu
      Abstract: Tilianin is an active flavonoid glycoside found in many medical plants. Data are lacking regarding its pharmacokinetics and disposition in vivo. The objective of this study was to develop a sensitive, reliable, and validated ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method to simultaneously quantify tilianin and its main metabolites and to determine its pharmacokinetics in wild-type and breast cancer resistance protein knockout (Bcrp1-/-) FVB mice. Chromatographic separation was accomplished on a C18 column by utilizing acetonitrile and 0.5 mM ammonium acetate as the mobile phase. Mass spectrometric detection was performed using electrospray ionization in both positive and negative modes. The results showed that the precision, accuracy, and recovery, as well as the stability of tilianin and its metabolites in mouse plasma were all within acceptable limits. Acacetin-7-glucuronide (Aca-7-G) and acacetin-7-sulfate (Aca-7-S) were the major metabolites of tilianin in mouse plasma. Moreover, systemic exposure of Aca-7-S was significantly higher in Bcrp1 (-/-) FVB mice compared with wild-type FVB mice. In conclusion, the fully validated UHPLC-MS/MS method was sensitive, reliable, and successfully applied to assess the pharmacokinetics of tilianin in wild-type and Bcrp1 (-/-) FVB mice. BCRP had a significant impact on the elimination of the sulfated metabolite of tilianin in vivo.
      PubDate: 2017-11-16T08:35:19.851686-05:
      DOI: 10.1002/bmc.4139
  • Determination of tubuloside B by LC–MS/MS and its application to a
           pharmacokinetic study in rats
    • Authors: Shenbao Yang; Ruiying Qu, Peilu Sun, Shan Xiong, Siyi Yan, Zhipeng Deng
      Abstract: Tubuloside B, a novel neuroprotective phenylethanoid, is a major active constituent of Cistanche tubulosa and Cistanche deserticola. A specific and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantification of tubuloside B in rat plasma. Sample preparation was conducted through a protein-precipitation extraction with methanol using tubuloside A as internal standard (IS). Chromatographic separation was achieved by using a Capcell Pak C18 column (2.0 mm × 50 mm, 5 μm) with a mobile phase of methanol-10 mM ammonium acetate buffer (70:30, v/v) in an isocratic elution way. Mass spectrometry (MS) analysis was performed in negative ionization mode with selection reaction monitoring (SRM) transitions at m/z 665.1 160.9 for tubuloside B, and m/z 827.1 160.9 for IS. Calibration curves were linear over the ranges of 1.64–1640 ng/mL for plasma samples samples (R2> 0.990). The lower limit of quantification (LLOQ) was 1.64 ng/mL. The intra-day and inter-day accuracy was between 92.3% and 113.0% with the RSD less than 9.23% at all LLOQ and QC levels. Finally, this method was successfully applied in the pharmacokinetics study of tubuloside B after intravenous administration.
      PubDate: 2017-11-16T08:21:50.264101-05:
      DOI: 10.1002/bmc.4138
  • Sample Preparation for Large Scale Bioanalytical Studies Based on Liquid
           Chromatographic Techniques
    • Authors: Andrei Medvedovici; Elena Bacalum, Victor David
      Abstract: Quality of the analytical data obtained for large-scale and long term bioanalytical studies based on liquid chromatography depends on a number of experimental factors including the choice of sample preparation method. This review discusses this tedious part of bioanalytical studies, applied to large scale samples and using liquid chromatography coupled with different detector types as core analytical technique. The main sample preparation methods included in this paper are protein precipitation, liquid-liquid extraction, solid-phase extraction, derivatization, and their versions. They are discussed by analytical performances, fields of applications, advantages and disadvantages. The cited literature covers mainly the analytical achievements during the last decade, although several previous papers became more valuable in time and they are included in this review.
      PubDate: 2017-11-16T07:15:20.386527-05:
      DOI: 10.1002/bmc.4137
  • A novel fast method for aqueous derivatization of THC, OH-THC and THC-COOH
           in human whole blood and urine samples for routine forensic analyses.
    • Authors: Fabio Stefanelli; Federica Giorgia Pesci, Mario Giusiani, Silvio Chericoni
      Abstract: A novel aqueous in situ derivatization procedure with propyl chloroformate (PCF) for the simultaneous, quantitative analysis of Δ9-tetrahydrocannabinol (THC), 11-hydroxy-Δ9-tetrahydrocannabinol (OH-THC) and 11-nor-Δ9-tetrahydrocannabinol-carboxylic acid (THC-COOH) in human blood and urine is proposed.Unlike current methods based on the silylating agent (BSTFA) added in an anhydrous environment, this new proposed method allows to add the derivatizing agent (propyl chloroformate, PCF) directly to the deproteinized blood and recover the derivatives by liquid-liquid extraction. This novel method can be also used for hydrolyzed urine samples, which is faster than the traditional method involving a derivatization with trimethyloxonium tetrafluoroborate (TMO).The analytes are separated, detected and quantified by gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring mode (SIM). The method was validated in terms of selectivity, capacity of identification, limits of detection (LOD) and quantification (LOQ), carryover, linearity, intra-assay precision, inter-assay precision and accuracy.The limits of detection (LOD) and quantification (LOQ) in hydrolyzed urine were 0.5 ng/mL and 1.3 ng/mL for THC and 1.2 ng/mL and 2.6 ng/mL for THC-COOH, respectively. In blood, the LOD and LOQ were 0.2 ng/mL and 0.5 ng/mL for THC, 0.2 ng/mL and 0.6 ng/mL for OH-THC, 0.9 ng/mL and 2.4 ng/mL for THC-COOH, respectively.This method was applied to thirty-five urine samples and fifty blood samples resulting to be equivalent to the current ones with the advantage of a more simple and faster sample processing time. We believe it will be a more convenient option for the routine analysis of cannabinoids in toxicological and forensic laboratories.
      PubDate: 2017-11-14T08:16:36.089091-05:
      DOI: 10.1002/bmc.4136
  • Analysis and Measurement of Serotonin
    • Authors: András Seitz; Stelvio M. Bandiera
      Abstract: Serotonin, also known as 5-hydroxytryptamine, is an important signaling molecule in the central and peripheral nervous systems of humans. Acting through several receptor types, it helps regulate the normal functioning of the gastrointestinal tract, cardiovascular system and brain. Serotonin signaling has also been implicated in the etiology of several diseases, including depression, anxiety disorders, hypertension and irritable bowel syndrome. The present review focuses on the chemical analysis of serotonin in biological fluids and biomatrices and traces the development and application of early methods based on UV absorbance or fluorescence to more widely-used current methods such as high-performance liquid chromatography coupled to mass spectrometry. A brief summary of the biochemistry, metabolism and physiological roles of serotonin is also presented.
      PubDate: 2017-11-14T07:55:20.547073-05:
      DOI: 10.1002/bmc.4135
  • Analytical approach, dissipation pattern, and risk assessment of pesticide
           residue in green leafy vegetables: A comprehensive review
    • Authors: Waziha Farha; A.M. Abd El-Aty, Md. Musfiqur Rahman, Ji Hoon Jeong, Ho-Chul Shin, Jing Wang, Sung Shik Shin, Jae-Han Shim
      Abstract: The category of “leafy vegetables” comprises a wide range of plants, including cabbage, lettuce, leeks, spinach, Swiss chard, and kale, and it forms a significant component of the human diet. Typically, leafy vegetables are low in calories and fat, are great sources of vitamins, protein, dietary fibre, minerals (including iron, calcium, and nitrates), and are rich in phytochemicals. To counter the impact of pests on vegetables, a broad variety of pesticides is used. Because of their large surface areas, leafy vegetables are expected to have high residual pesticide levels. As such, a sound analytical approach was necessary to detect and quantify residue levels that are equal to or lower than the maximum residue limits (MRL), thus rendering the products safe for consumption. Overall, leafy vegetables consumed raw (after a tap water wash only), boiled, or steamed contribute 2% of total vegetable consumption globally, and they might have a comparatively greater influence on health than that of cereal ingestion. Consequently, in this review paper, we highlight the importance of leafy vegetables, the pesticides that are commonly used on them, and various analytical techniques, including sample preparation, extraction, clean-up, and final detection. The effects on dissipation patterns, pre-harvest residue limits, and safety/risks imposed by various pesticides are also reviewed and discussed. In conclusion, environmentally-friendly extraction methods coupled with high throughput techniques with greater reproducibility and lower uncertainty are needed for quantifying residues in leafy vegetables at very low concentrations. Commercial and household food preparation, such as washing, peeling, blanching, and cooking are effective in removing most of the pesticide residues that are loosely attached on vegetables.
      PubDate: 2017-11-14T01:10:23.435941-05:
      DOI: 10.1002/bmc.4134
  • Chromatographic analysis of VOC patterns in exhaled breath from smokers
           and nonsmokers
    • Authors: Simonetta Capone; Maria Tufariello, Angiola Forleo, Valentina Longo, Lucia Giampietruzzi, Antonio Vincenzo Radogna, Flavio Casino, Pietro Siciliano
      Abstract: Cigarette smoking harms nearly every organ of the body and causes many diseases. The analysis of exhaled breath for exogenous and endogenous Volatile Organic Compounds (VOCs) can provide fundamental information on active smoking and insight into the health damage that smoke is creating. Various exhaled Volatile Organic Compounds (VOCs) have been reported as typical of smoking habit and recent tobacco consumption, but to date, no eligible biomarkers have been identified. Aiming to identify such potential biomarkers, in this pilot study we analysed the chemical patterns of exhaled breath from 26 volunteers divided in groups of nonsmokers and subgroups of smokers sampled at different periods of withdrawal from smoking. Solid Phase MicroExtraction technique (SPME) and Gas Chromatography/Mass Spectrometry (GC/MS) method were applied.Many breath VOCs were identified and quantified in very low concentrations (ppbv range), but only a few (toluene, pyridine, pyrrole, benzene, 2-butanone, 2-pentanone, 1-methyldecyclamine) were found to be statistically significant variables by Mann-Whitney test. In our analysis, we didn’t consider the predictive power of individual VOCs, as well as the criterion of uniqueness for biomarkers suggests, but on the contrary, we used the patterns of the only statistically significant compounds. Probit prediction model based on statistical relevant VOCs-patterns showed that assessment of smoking status is heavily time dependent; it's possible recognise with high specificity and sensitivity smokers after a short-term exposure to tobacco (i.e. after 1 hour of smoking abstinence), whereas smokers after a long-term exposure to tobacco (i.e. after a night out of smoking) are more like non-smokers.
      PubDate: 2017-11-13T08:35:20.597493-05:
      DOI: 10.1002/bmc.4132
  • Method development for Quantification of Quizartinib in Rat Plasma by
           Liquid Chromatography/Tandem Mass Spectrometry for pharmacokinetic
    • Authors: Essam Ezzelddin; Muzaffar Iqbal, Gamal Mostafa, Khalid A. Al-Rashood, Toqa El nahhas
      Abstract: Quizartinib is a highly potent inhibitor of the fms-like tyrosine kinase receptor, which is one of the most commonly mutated genes in acute myeloid leukemia (AML). Quizartinib has shown a significant antileukemic clinical influence among relapsed/refractory acute AML patients. This study aimed at developing and validating an analytical method for the measurement of quizartinib in rat plasma using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The method was validated according to FDA guidelines, and the results obtained in this work met the set criteria. Liquid–liquid extraction was used and chromatographic separation was achieved on a BEHTM C18 column. Detection of quizartinib was achieved in the multiple reaction monitoring mode using positive-ion mode electrospray ionization. The MS/MS ion transitions at mass-to-charge ratios (m/z) of 561.129/114.09 and 441.16/84.03 were monitored for quizartinib and ibrutinib, respectively. The linear detection range was 2–1000 ng/mL (r> 0.998), with intraand inter-day assay precisions equal to or less than 13.07% and 13.17%, respectively. This rapid, simple, and sensitive method was validated and successfully applied to the pharmacokinetic study of quizartinib in rat samples.
      PubDate: 2017-11-13T08:15:27.53241-05:0
      DOI: 10.1002/bmc.4131
  • Combined Metabolomic and Correlation Networks Analyses Reveal Fumarase
           Insufficiency Altered Amino Acids Metabolism
    • Authors: Entai Hou; Xian Li, Zerong Liu, Fuchang Zhang, Zhongmin Tian
      Abstract: Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. Fumarase insufficiencies were associated with increased level of fumarate and decreased level of malate and exacerbated salt-induced hypertension. To gain insights into the metabolism profiles that induced by fumarase insufficiency and identify key regulatory metabolites, we applied a GC–MS based metabolomics platform coupled with a network approach to analyze fumarase insufficient HUVEC cells and negative controls. A total of 24 altered metabolites involved in 7 metabolic pathways were identified as significantly altered, and enriched for the biological module of amino acids metabolism. In addition, Pearson correlation network analysis revealed that fumaric acid, L-malic acid, L-aspartic acid, glycine and L-glutamic acid were hub metabolites according to Pagerank based on their three centrality indices. ALT and GDH activities increased significantly in fumarase deficiency HUVEC cells. These results confirmed that fumarase insufficiency altered amino acid metabolism. The combination of metabolomics and network methods would provide another perspective on expounding the molecular mechanism at metabolomics level.
      PubDate: 2017-11-11T10:20:33.490875-05:
      DOI: 10.1002/bmc.4133
  • Simultaneous determination and pharmacokinetic study of giraldoid A,
           giraldoid B in rat plasma after oral administration of Daphne giraldii
           Nitsche extracts by LC-MS/MS
    • Authors: Huyiligeqi; Xiaoxv Dong, Jing Fu, Sali Cao, Chunjing Yang, Longtai You, Zhongyi Zhang, Jian Ni
      Abstract: A simple sensitive LC-MS/MS method has been developed for the simultaneous determination of giraldoid A and giraldoid B in rat plasma. The method was applied to the pharmacokinetics studies of the two compounds from Daphne giraldii Nitsche. Chromatographic separation was accomplished on an ACQUITY UPLC™ BEH C18 column (100 × 2.1 mm, 1.7 mm) by gradient elution with a flow rate of 0.2 mL min-1. The method was linear over the concentration range of 1.0-1000 ng mL-1, and the lower limit of quantification were 1.04 ± 0.10, 1.04 ± 0.09 ng mL-1, respectively. The intra- and inter-day precisions (RSD) were less than 10.14 and 9.96 %. The extraction recovery of the analytes was acceptable. Stability studies demonstrated that the two compounds were stable in the preparation and analytical process. The maximum plasma concentration (Cmax) was 687.78 ± 243.62 ng mL-1 for giraldoid A and 952.38 ± 131.99 ng mL-1 for giraldoid B, respectively. The time to reach the maximum plasma concentration (Tmax) was 0.50 ± 0.37 h for giraldoid A and 0.50 ± 0.66 h for giraldoid B, respectively. The validated method was successfully applied to investigate the concentration-time profiles of giraldoid A and giraldoid B.
      PubDate: 2017-11-07T00:00:45.361948-05:
      DOI: 10.1002/bmc.4129
  • Simultaneous determination and tissue distribution studies of four
           phenolic acids in rat tissue by UFLC-MS/MS after intravenous
           administration of salvianolic acid for injection
    • Authors: Shuang Li; Xiuman Xie, Dongxiang Li, Zhiguo Yu, Ling Tong, Yunli Zhao
      Abstract: A rapid, simple and sensitive ultra-fast liquid chromatography tandem mass spectrometric method was developed and validated for simultaneous determination and tissue distribution studies of rosmarinic acid, salvianolic acid D, lithospermic acid and salvianolic acid B in rats after intravenous administration of salvianolic acid for injection. The tissue homogenate samples were pretreated by protein precipitation with pre-cooled acetonitrile. Chromatographic separation was achieved on a Waters Cortecs UPLC C18 column (1.6 μm, 2.1 × 100 mm) with a mobile phase composed of 0.1% formic acid-water and 0.1% formic acid-acetonitrile. Analytes were detected by electrospray ionization mass spectrometry and quantitated using multiple reaction monitoring. The method was fully validated. The calibration curves for the four phenolic acids were linear in the given concentration ranges. The precision (relative standard deviation) in the measurement of quality control samples were less than 10% and the accuracy (relative error) were in the range of 0.28%-11.22%. The reliable method was successfully applied to the tissue distribution studies of the four phenolic acids. The results showed that rosmarinic acid, salvianolic acid D, lithospermic acid and salvianolic acid B were rapidly distributed in tissues with the major amount found in kidney, and little amount crossed the blood-brain barrier. The developed method and the results can provide a basis for further studies.
      PubDate: 2017-11-06T02:51:36.395902-05:
      DOI: 10.1002/bmc.4128
  • Pharmacokinetics of Pidotimod in Broiler Chickens by UHPLC-MS/MS after
           Oral and Intravenous Administration
    • Authors: Ruili Zhang; Mei Qiu, Li Zhao, Liangliang Cui, Chunyuan Wang, Jiajia Zhu, Zhihui Hao
      Abstract: Pidotimod is widely used in children as an immune promoter but it has not been fully evaluated in animals. Pharmacokinetics of pidotimod and its oral bioavailability have not been described in broiler chickens. We developed a simple and sensitive UHPLC-MS/MS assay for rapid determination of pidotimod levels in chicken blood. Recoveries were nearly 100% and the coefficients of accuracy and precision were minimal. Healthy broiler chickens were given 10 mg/kg pidotimod either orally or intravenously. The oral pidotimod was rapidly absorbed [time of reaching maximum concentration (tmax) 1.25h] and rapidly eliminated (the mean residence times was 3.2h) A noncompartmental analysis of the intravenous route indicated a mean plasma clearance of 2.2 L· (h·kg)-1 with an estimated mean volume of distribution at steady-state of 12.69 L/kg. Bioavailability of pidotimod after oral dosing was 27%.
      PubDate: 2017-11-06T02:51:34.271824-05:
      DOI: 10.1002/bmc.4130
  • Proteomics analysis of altered proteins in kidney of mice with
           aristolochic acid nephropathy using the fluorogenic derivatization-liquid
           chromatography-tandem mass spectrometry method
    • Authors: Chia-En Lin; Wen-Shin Chang, Jen-Ai Lee, Ting-Ya Chang, Yu-Shen Huang, Yoshiro Hirasaki, Hung-Shing Chen, Kazuhiro Imai, Shih-Ming Chen
      Abstract: Aristolochic acid (AA) causes interstitial renal fibrosis, which called aristolochic acid nephropathy (AAN). There is no specific indicator for diagnosing AAN, so this study was to investigate the biomarkers for AAN using a proteomics method. The C3H/He female mice were given ad libitum AA-distilled water (0.5 mg/kg/day) and distilled water for 56 days in the AA and normal groups, respectively. The AA-induced proteins in the kidney were investigated using a proteomics study, including fluorogenic derivatization with 7-chloro-N-[2-(dimethylamino)ethyl]-2,1,3- benzoxadiazole-4-sulfonamide (DAABD-Cl), and followed by high performance liquid chromatography analysis and liquid chromatography tandem mass spectrometry (FD-LC-MS/MS) with a MASCOT database searching system. There were two altered proteins, thrombospondin type 1 (TSP1) and G protein-coupled receptor 87 (GPR87), in the kidney of AA-group mice on day 56. GPR87, tumorigenesis-related protein, was newly reported in the current study. The renal interstitial fibrosis was certainly induced in the AA-group mice under the observation of histological examination. Based on the results of histological examination and proteomics study, this model might be applied to AAN studies in the future. TSP1 might be a novel biomarker for AAN, and the further role of GPR87 leading to AA-induced tumorigenesis should be researched in future studies.
      PubDate: 2017-10-31T13:00:20.439785-05:
      DOI: 10.1002/bmc.4127
  • A sensitive LC-MS/MS method for simultaneous quantification of geniposide
           and its active metabolite genipin in rat plasma and its application to a
           pharmacokinetic study
    • Authors: Fuguo Shi; Hong Pan, Yi Li, Linyan Huang, Qin Wu, Yuanfu Lu
      Abstract: Genipin (GP), an active metabolite of geniposide (GE), exhibited more potent pharmacological effects than its parent compound. In this paper, a sensitive LC-MS/MS method was developed and fully validated for the simultaneous determination of GE and GP in rat plasma. We found GP degraded rapidly in rat plasma at room temperature as a result of the irreversible binding with the endogenous nucleophiles in plasma. GP is stable when the samples pH is less than or equal to 4.0. The degradation of GP in rat plasma was well prevented by immediate addition of 5% glacial acetic acid to the freshly collected plasma. The detection was performed on a tandem mass spectrometer coupled with electrospray ionization source in negative mode. Quantification was conducted by multiple reaction monitoring of the transitions of at [M+CH3COO]- m/z 447.3225.3 for GE, and at [M-H]- m/z 225.2123.1 for GP. The method exhibited high sensitivity (LLOQ of 1 ng/mL for GE and 0.2 ng/ml for GP) by selecting the acetate adduct ions as the precursor ion for GE. The robust developed method was successfully applied to a pharmacokinetic study in rats after oral administration of GE.
      PubDate: 2017-10-31T12:30:23.344027-05:
      DOI: 10.1002/bmc.4126
  • Simultaneous separation and analysis of camptothecin alkaloids in real
           samples by large volume sample stacking in capillary electrophoresis
    • Authors: Meng Chen; Yayun Huang, Liying Xu, Hongfen Zhang, Guangbin Zhang, Anjia Chen
      Abstract: Large-volume Sample Stacking (LVSS) is commonly used as an effective on-line preconcentration method in capillary zone electrophoresis (CZE). In this paper, the method LVSS combined with CZE has been proposed to analysis the camptothecin alkaloids. Optimum separation can be achieved in conditions as following: pH 9.0, 25 mM borate buffer containing 20 mM Sulfobutylether-β-Cyclod-extrin (SBE-β-CD) and 20 mM ionic liquid [EMIM] [L-Lac] (IL), the applied voltage was 20 kV and the capillary temperature was 25°C. The LVSS was optimized as hydrodynamic injection 4 s at 5.0 psi and the polarity switching time was 0.17 min. Under the above conditions, the analytes could be separated completely in less than 20 min and the detector response had been increased compared with conventional hydrodynamic injection. The limit of detection were between 0.20 and 0.78 μg/L. A good linearity could be obtained with correlation coefficients from 0.9991 to 0.9997. The recoveries ranged from 97.72 to 103.2% and the results demonstrated excellent accuracy. In terms of the migration time and peak area, the experiment was reproducible. And the experimental results indicated that baseline separation can be obtained and this method is suitable for the quantitative determination of camptothecin alkaloids in real samples.
      PubDate: 2017-10-31T11:40:22.293711-05:
      DOI: 10.1002/bmc.4125
  • A sensitive HPLC-MS/MS method for the simultaneous determination of
           Anemoside B4, Anemoside A3 and 23-hydroxybetulinic acid: application to
           the pharmacokinetics and liver distribution of Pulsatilla chinensis
    • Authors: Xiaozhen Guo; Yang Xie, Shan Lian, Zhixiong Li, Yu Gao, Zhou Xu, Pei Hu, Mingcang Chen, Zhaolin Sun, Xiaoting Tian, Chenggang Huang
      Abstract: Pulsatilla chinensis saponins, the major active components in the herb, have drawn great attention as potential hepatitis B virus infection and hepatoma treatments. Here, a sensitive and accurate HPLC-MS/MS method was established for simultaneous determination of three saponins, Anemoside B4, Anemoside A3 and 23-hydroxybetulinic acid, in rat plasma and liver, and fully validated. The method was successfully applied to the pharmacokinetics and liver distribution study of Pulsatilla chinensis saponins. Consequently, 23-hydroxybetulinic acid, with an extremely low content in the P. chinensis saponins, exhibited the highest exposure in the liver and in sites before and after hepatic disposition, namely, in the portal vein plasma and systemic plasma, followed by Anemoside B4, which was of the highest content in the herb, whereas Anemoside A3 displayed quite limited exposure. The hepatic first-pass effects were 71% for 23-hydroxybetulinic acid, 27% for Anemoside B4 and 37% for Anemoside A3, corresponding to their different extent of liver distribution. To our knowledge, this is the first investigation on the liver first-pass effect and distribution of Pulsatilla chinensis saponins to date. These results also provide valuable information for the understanding of the pharmacological effect of Pulsatilla chinensis saponins on liver diseases.
      PubDate: 2017-10-27T16:20:27.04103-05:0
      DOI: 10.1002/bmc.4124
  • Preparation and evaluation of a chiral HPLC stationary phase based on cone
           calix[4]arene functionalized at the upper rim with L-alanine units
    • Authors: Sadegh Yaghoubnejad; Kourosh Tabar Heydar, Seyyed Hamid Ahmadi, Reza Zadmard
      Abstract: Here we report a new chiral stationary phase (CSP) immobilized on silica gel based on cone calix[4]arene functionalized at the upper rim with two L-alanine units as new chiral selector that has been used in high performance liquid chromatography. The CSP was prepared by covalently bonding the allyl groups at the lower rim of calix[4]arene to silica gel by thiol-ene click chemistry reaction. Elemental analysis of the CSP showed that 120 μmol of chiral selector bonded per gram of silica gel. 1-Hexene was used for end-capping of unreacted mercapto groups on silica gel. Since the CSP is chemicaly bonded to the silica, it can be used in the normal-phase mode, reversed-phase mode and with halogenated solvents mobile phases, if desired. The chromatographic performance of the CSP was evaluated in the enantioseparation of the 3,5-dinitrobenzoyl (DNB) derivatives of some amino acids, diclofop-methyl, and DL-mandelic acid.
      PubDate: 2017-10-23T14:25:20.967583-05:
      DOI: 10.1002/bmc.4122
  • Simultaneous Determination of Usnic, Diffractaic, Evernic and Barbatic
           Acids in Rat Plasma by Ultra High Performance Liquid
           Chromatography-Quadrupole Exactive Orbitrap Mass Spectrometry and Its
           Application to Pharmacokinetic Studies
    • Authors: Hanxue Wang; Tao Yang, Xuemei Cheng, Sukfan Kwong, Chenghai Liu, Rui An, Guowen Li, Xinhong Wang, Changhong Wang
      Abstract: Usnea longissima Ach. (Usnea) has been used in pharmaceuticals, food, cosmetics. Evernic acid (EA), barbatic acid (BA), diffractaic acid (DA), and usnic acid (UA) are the most typical ingredients in U. longissima and exert a wide variety of biological functions. The study aim to develop a sensitive method for simultaneous analysis of EA, BA, DA, and UA in rat plasma and applied to pharmacokinetic studies after consumption of UA and ethanol extract from U. longissima (UE). The samples were separated on BEH C18 column by gradient elution with 0.5% formic acid in water and in methanol. The relative molecular masses of analytes were obtained in full scan range from 50.0 to 750.0 m/z under negative ionization mode by UPLC-Q-Exactive Orbitrap MS. All validation parameters, such as lower limit of quantitation, linearity, specificity, precision, accuracy, extraction recovery, matrix effect and stability, within acceptable ranges and the method was appropriate for biological specimen analysis. The pharmacokinetics results indicated that the absolute bioavailability of UA after oral administration of UA and UE reaches 69.2% and 146.9%, respectively. Comparing to UA in UE, the relative bioavailability of DA, BA and EA reaches 103.7%, 10.4%, and 0.7% after oral administration of UE.
      PubDate: 2017-10-21T00:20:23.851016-05:
      DOI: 10.1002/bmc.4123
  • Identification of absorbed constituents and in vivo metabolites in rats
           after oral administration of Physalisalkekengi var. franchetii by
           ultrahigh-pressure liquid chromatography quadrupole time-of-flight mass
    • Authors: Xinchi Feng; Xiaoguang Huo, Hongxia Liu, Liwei Chai, Liqin Ding, Feng Qiu
      Abstract: The calyces of Physalisalkekengi var. franchetii (Chinese Lantern, JDL) are well-known traditional Chinese medicine owing to its various therapeutic effects. However, the bioactive constituents responsible for the pharmacological effects of JDL and their metabolites in vivo are still unclear to date. In this paper, an ultrahigh-pressure liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/Q–TOF–MS/MS) method was established to identify absorbed constituents and in vivo metabolites in rat biological fluids after oral administration of JDL. Based on the proposed strategy, 33 compounds were observed in dosed rat biosamples. 12 of 33 compounds were indicated as prototype components of JDL, and 21 compounds were predicted to be metabolites of JDL. Finally, the metabolic pathways were proposed, which were the glucuronidation, sulfation, methylation and dehydroxylation for flavonoids constituents and sulfonation and hydroxylation for physalins consitituents. This is the first systematic study on the absorbed constituents and metabolic profiling of JDL and will provide a useful template for screening and characterizing the ingredients and metabolites of traditional Chinese medicine.
      PubDate: 2017-10-20T22:35:34.089163-05:
      DOI: 10.1002/bmc.4121
  • Retention behavior of flavonoids on Immobilized Artificial Membrane
           Chromatography and correlation with cell- based permeability
    • Authors: Fotios Tsopelas; Maria Tsagkrasouli, Pavlos Poursanidis, Maria Pitsaki, George Vasios, Panagiotis Danias, Irene Panderi, Anna Tsantili- Kakoulidou, Constantinos Giaginis
      Abstract: The aim of the study was to investigate IAM retention mechanism for a set of flavonoids and to evaluate the potential of IAM chromatography to model Caco-2 permeability. For this purpose, the retention behavior of 41 flavonoid analogues on two immobilized artificial membrane (IAM) stationary phases, IAM.PC.MG and IAM.PC.DD2, was investigated. Correlations between retention factors, logkw(IAM) and octanol- water partitioning (logP) were established and the role of hydroxyl groups of flavonoids to the underlying retention mechanism was explored. IAM retention and logP values were used to establish sound linear models with Caco-2 permeability (logPapp) taken from the literature. Both stepwise regression and multivariate analysis confirmed the contribution of hydrogen bond descriptors, as additional parameters in the either logkw(IAM) or logP models. Retention factors on both IAM stationary phases showed comparable performance with n-octanol- water partitioning towards Caco-2 permeability.
      PubDate: 2017-10-18T03:25:21.716949-05:
      DOI: 10.1002/bmc.4108
  • Characteristic components profiling and identification of different
           Uncaria species based on high performance liquid chromatography-photodiode
           array detector tandem ion trap and time of flight mass spectrometer
           coupled with rDNA ITS sequence
    • Authors: Bingqiang Zhao; Yanjun Huang, Qiulan Chen, Qizhao Chen, Hui Miao, Shuang Zhu, Changqing Zeng
      Abstract: The Uncaria is a multi-source herb and its species identification has become a bottleneck in quality control. To study the identification method of different Uncaria species herbs through HPLC-MS coupled with rDNA Internal Transcribed Spacer (rDNA ITS) sequence, both plant morphological traits and molecular identification were used to determine the species of every collected Uncaria herbs. The genetic analysis of different Uncaria species was performed by using their rDNA ITS sequence as a molecular marker. Meanwhile, the phylogenetic relationships of 22 samples from six Uncaria species were divided and classified clearly. By optimizing the chromatographic conditions, a practical HPLC method to differentiate various varieties of Uncaria herbs was set up based on a set of characteristic components across each species. A high-performance liquid chromatography-photodiode array detector tandem ion trap and time of flight mass spectrometer (LCMS-IT-TOF) technique combined with reference substances was utilized to derive 21 characteristic compounds containing six groups of six Uncaria species in China. Thus, this study provides a feasible method to solve the current problem of confusion in Uncaria species, and makes a significant step forward in the appropriate clinical use, in-depth research, and further utilization of different Uncaria species.
      PubDate: 2017-10-16T00:51:02.909148-05:
      DOI: 10.1002/bmc.4119
  • Determination of Thiocyanate as a Biomarker of Tobacco Smoke Constituents
           in Selected Biological Materials of Human Origin
    • Authors: Sylwia Narkowicz; Ewa Jaszczak, Żaneta Polkowska, Bogumiła Kiełbratowska, Alicja Kotłowska, Jacek Namieśnik
      Abstract: In order to protect human health, it is necessary to biomonitor toxic substances originating from tobacco smoke in biological materials sampled from the persons with different exposures to tobacco smoke constituents. Thiocyanate anion is a biomarker of exposure to tobacco smoke components which is characterized by a relatively long half-life in the human body, i.e. 6 days. In this work, we present the results of thiocyanate determinations performed on the samples of placenta, meconium, saliva, breast milk, sweat and blood. The placenta samples were subjected to accelerated solvent extraction with water. The thiocyanate concentrations were determined by using ion chromatography. The analyzed biological materials were compared with regard to their applicability for biomonitoring toxic substances originating from tobacco smoke. The highest mean concentrations of thiocyanate were observed in the samples of biological materials collected from active smokers.
      PubDate: 2017-10-13T04:26:23.81266-05:0
      DOI: 10.1002/bmc.4111
  • Chemical interaction between Lilium brownii and Rhizoma Anemarrhenae, the
           herbal constituents of Baihe Zhimu decoction, by liquid chromatography
           coupled to hybrid triple quadrupole linear ion trap mass spectrometer
    • Authors: Bo Yang; Zhirui Liu, Qian Wang, Peiyuan Xia
      Abstract: During the course of decoction, the components of herbal formula interact with each other, such that chemical extraction characteristics are altered. The crude drugs, Lilium brownii (Baihe) and Rhizoma Anemarrhenae (Zhimu), are the herbal constituents of Baihe Zhimu decoction, a traditional herbal formula. To investigate the chemical interaction between Baihe and Zhimu when decocting together, eight marker components in Baihe Zhimu decoction were simultaneously characterized and quantified in one run by a hybrid triple quadrupole linear ion trap mass spectrometer in the multiple reactions monitoring-information dependent acquisition-enhanced product ion (MRM-IDA-EPI) mode. The results showed that Zhimu significantly suppressed the extraction of phenolic glycosides (the components from Baihe) when co-decocting, and Baihe clearly suppressed the extraction of xanthones and steroidal saponins (the components from Zhimu). Overall, the presently developed method would be a preferred candidate for the investigation of the chemical interaction between herbal medicines.
      PubDate: 2017-10-13T04:26:03.434539-05:
      DOI: 10.1002/bmc.4118
  • Toxicokinetics of strychnine and brucine after the oral administration of
           Biqi capsule to rats by RRLC-MS/MS
    • Authors: Hao Zheng; Zhe Wang, Wenwei Liu, Hongtao Jin, Jinlan Zhang
      Abstract: Biqi capsule is a well-known traditional Chinese medicine (TCM) formula that has been widely applied for the clinical treatment of such diseases as rheumatoid arthritis, scapulohumeral periarthritis, and cervical spondylopathy. However, there is concern regarding the toxicity of Biqi capsule due to its active ingredients, strychnine and brucine. To investigate the toxicokinetics of strychnine and brucine after the oral administration of Biqi capsule to rats, a sensitive and simple rapid-resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS) method was developed to determine the levels of strychnine and brucine in rat plasma. Chromatographic separation was performed on a CAPCELL PAK C18 MG II (3.0 μm, 2.0×35 mm) column by gradient elution with acetonitrile and 0.2% formic acid as the mobile phase. The method was validated over the range of 0.25 to 250 ng/mL for strychnine and 0.025 to 25 ng/mL for brucine. The intra- and inter-day accuracies of strychnine and brucine in rat plasma were 100.3%-106.6% and 90.75%-106.1% respectively, and the precisions were within 14.2%. The established method was successfully applied to the toxicokinetic study of strychnine and brucine after single and multiple oral administration of Biqi capsule to male and female rats at 0.4-, 0.8-, and 1.6-g/kg doses. The results showed different toxicokinetic characteristics in the different groups.
      PubDate: 2017-10-13T04:25:51.779297-05:
      DOI: 10.1002/bmc.4117
  • Comparison of Plasma Pharmacokinetics of Tanreqing Solution between
           Intratracheal Aerosolization and Intravenous Injection in Rats
    • Authors: Cui Li; Siyu Liu, Gan Luo, Guohua Wang, Baoxian Zhang, Qixia Nie
      Abstract: A rapid ultra high performance liquid chromatography tandem mass spectrometry method was developed for the simultaneous analysis of baicalin, oroxylin A-7-O-β-D-glucoronide and chlorogenic acid in rats plasma, and it was applied to comparison of pharmacokinetics of Tanreqing solution between intratracheal aerosolization and intravenous injection. Results of the analytical method validation assay showed high sensitivity, accuracy and suitable recovery. Results of pharmacokinetics showed a similar decline phase for baicalin, oroxylin A-7-O-β-D-glucoronide and chlorogenic acid in two different delivery routes. The T1/2 (h) of intratracheal aerosolization and intravenous injection are 0.90 and 1.22 for baicalin, 0.47 and 0.17 for oroxylin A-7-O-β-D-glucoronide, 0.22 and 0.13 for chlorogenic acid, and implies that compounds was retained in the lung for a relatively short time. This study was the first to provide important pharmacokinetics information for traditional Chinese medicine delivery to the lung.
      PubDate: 2017-10-13T04:25:45.229735-05:
      DOI: 10.1002/bmc.4116
  • UPLC-HR-MS/MS-based determination study on the metabolism of four
           synthetic cannabinoids ADB-FUBICA, AB-FUBICA, AB-BICA and ADB-BICA, by
           human liver microsomes
    • Authors: Jing Li; Cuimei Liu, Tao Li, Zhendong Hua
      Abstract: Since 2012, several cannabimimetic indazole and indole derivatives with valine amino acid amide residue have emerged in the illicit drug market, and gradually replaced the old generations of synthetic cannabinoids (SCs) with naphthyl or adamantine groups. Among them, ADB-FUBICA, AB-FUBICA, AB-BICA and ADB-BICA were detected in China recently, but unfortunately no information about their in vitro human metabolism is available for now. Therefore, biomonitoring studies to screen their consumption lack any information about the potential biomarkers (e.g.metabolites) to target. To bridge this gap, we investigated their phase I metabolism by incubating with human liver microsomes, and the metabolites were identified by Ultra Performance liquid chromatography-high resolution-tandem mass spectrometry (UPLC-HR-MS/MS).Metabolites generated by N-dealkylation and hydroxylation on the 1-amino-alkyl moiety were found to be predominant for all these four substances, and others which underwent hydroxylation, amide hydrolysis and dehydrogenation were also observed in our investigation. Based on our research, we recommend that the N-dealkylation and hydroxylation metabolites are suitable and appropriate analytical markers for monitoring their intake.
      PubDate: 2017-10-09T12:10:20.758166-05:
      DOI: 10.1002/bmc.4113
  • Screening of analgesic and anti-inflammatory active component in Fructus
           Alpiniae zerumbet based on spectrum-effect relationship and GC-MS
    • Authors: Rui-yao Xiao; Ling-jing Wu, Xiao-xiao Hong, Ling Tao, Peng Luo, Xiang-chun Shen
      Abstract: Fructus Alpiniae zerumbet was widely used in Guizhou province as miao folk herb with anti-inflammatory, analgesic, protection against cardiovascular diseases, anti-hypertension, and antioxidant activities. To further investigate the chemical material basis, the spectrum-effect relationship was established using grey relational analysis between the chromatographic fingerprint and its bioactivities. Herein, the fingerprints of essential oils from Fructus Alpiniae zerumbet (EOFAZ) from various sources were determined by gas chromatography mass spectrometry (GC-MS), and the analgesic and anti-inflammatory bioactivities were investigated by the mice model of acetic acid-induced writhing test and dimethylbenzene-induced mice ear edema test. Finally, 17 common peaks were identified from 9 batches of Alpiniae zerumbet, by comparing with the standard mass spectra in Nist2005, Wiley275 library. Meanwhile, the results showed significant analgesic and anti-inflammatory effects all of the different resources of EOFAZ. In particularly, Peak 1 (alpha-pipene), peak 3 (beta-pinene), peak 9 (camphor) and peak 16 (alpha-cadinol) might be the main bioactive ingredients for analgesic and anti-inflammatory activities. The model of the spectrum–effect relationships of EOFAZ was successfully discovered, which provided a novel platform for finding the bioactive components, a theoretical foundation for its further study and helping for quality control of Fructus Alpiniae zerumbet.
      PubDate: 2017-10-09T10:30:59.251513-05:
      DOI: 10.1002/bmc.4112
  • A target and non-target strategy for identification or characterization of
           the chemical ingredients in Chinese herb preparation Shuang-Huang-Lian
           oral liquid by ultra-performance liquid chromatography-quadrupole
           time-of-flight mass spectrometry
    • Authors: Feng-xiang Zhang; Min Li, Zhi-hong Yao, Chang Li, Li-rui Qiao, Xiu-yu Shen, Kate Yu, Yi Dai, Xin-sheng Yao
      Abstract: A target and non-target strategy based on in-house chemical components library was developed for rapid and comprehensive analysis of complicated components from traditional Chinese medicine (TCM) preparation Shuang-Huang-Lian oral liquid (SHL). The sample was analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Qtof MS) using generic acquisition parameters. Automated detection and data filtering were performed on the UNIFITM software and the detected peaks were evaluated against an in-house library. As a result, a total of 170 chemical components (110 target compounds and 60 non-target ones) were identified or tentatively characterized, including 54 flavonoids, 30 phenylethanoid glycosides, 16 iridoid glycosides, 14 lignans, 32 organic acids, 19 triterpenoid saponins and 5 other types compounds. Among them, 44 compounds were further confirmed by comparison with reference standards. It demonstrated that this systematical approach could be successfully applied for rapid identification of multiple compounds in TCM and its preparations. Furthermore, this work established the foundation for the further investigation on the metabolic fates of multiple ingredients in SHL.
      PubDate: 2017-10-09T10:10:25.734863-05:
      DOI: 10.1002/bmc.4110
  • A review of bioanalytical quantitative methods for selected sphingosine
           1-phosphate (S1P1) receptor modulators
    • Authors: Ranjeet Prasad Dash; Nuggehally R. Srinivas, Rana Rais
      Abstract: Sphingosine 1-phosphate (S1P1) modulators provide an emerging therapeutic approach for various autoimmune disorders such as multiple sclerosis and psoriasis. Fingolimod is the first approved orally active, selective and potent drug of this class. Other drugs belonging to this class include siponimod, ponesimod, ceralifimod, amiselimod, CS-0777 and GSK2018682. However, due to the high protein binding, polarity and zwitter-ionic nature of the phosphate metabolite of parent drugs, it becomes challenging to optimize the extraction method for this class of compounds. Although, there are individual published bioanalytical methods for the analysis of selected S1P1 modulators to support preclinical and clinical drug development, no extensive review compiling all the bioanalytical methods for the important drugs in the class is available. Thus, we attempted to prepare a comprehensive review on various bioanalytical methods for selected S1P1 modulators which will provide all the relevant bioanalytical information as required by bioanalytical researchers. This review focuses on the various liquid chromatography with tandem mass spectrometry (LC-MS/MS) methods that have been used to quantify S1P1 modulators in various biological matrices. Extraction methods included liquid-liquid extraction, solid-phase extraction and one step protein precipitation for extracting the analytes. This review captures key information regarding sample processing options and chromatographic/detection conditions.
      PubDate: 2017-10-09T02:30:18.4958-05:00
      DOI: 10.1002/bmc.4109
  • Metabolite profiling of ginsenosides in rat plasma, urine, and faeces by
           LC-MS/MS and its application to a pharmacokinetic study after oral
           administration of Panax ginseng extract
    • Authors: Wei-Wei Dong; Xiong-Zhe Han, Jinhua Zhao, Fei-Liang Zhong, Rui Ma, Songquan Wu, Donghao Li, Lin-Hu Quan, Jun Jiang
      Abstract: Panax ginseng has been widely consumed as a functional food in the form of tea, powder, capsules, among others, and possesses a range of pharmacological activities including adaptogenic, immune-modulatory, anti-tumour, anti-aging, and anti-inflammatory effects. The aim of this study was to identify and quantify the major ginsenosides and their metabolites in rat plasma, urine, and faeces after administration of Panax ginseng extract by using LC–MS/MS. We collected rat plasma samples at 0.5, 1, 2, 4, 8, 12, 24, and 48 h, and the amounts of urine and faecal samples accumulated in 24 h. Fourteen major ginsenosides and their metabolites were observed in faecal samples at high levels; however, low levels of eleven ginsenosides were detected in urine samples. The pharmacokinetics of the major ginsenosides and their metabolites was investigated in plasma. The results indicated that Cmax, Tmax, and AUC of compound K were significantly greater than those of other ginsenosides. This study thus provides valuable information for drug development and clinical application of Panax ginseng.
      PubDate: 2017-10-07T09:00:28.015701-05:
      DOI: 10.1002/bmc.4105
  • Ketamine and Norketamine Stability in Whole Blood at Ambient and 4°C
    • Authors: Benjamin Duy Tran; Ganesh S. Moorthy, Athena F. Zuppa
      Abstract: A study was implemented to describe the pharmacokinetics (PK) of ketamine (K) and its metabolite norketamine (NK) in critically ill adults. Conducting studies in these subjects is hindered by the immediate need to process and freeze samples obtained in a busy intensive care setting. The ability to store unprocessed samples at room temperature for an extended time period would overcome this barrier. Stability and blood to plasma partitioning of K and NK were investigated in whole blood up to 120 h at room temperature and 4 °C. Whole blood was spiked with K and NK (1,000 ng/mL each). Blood samples were aliquoted at different time points (0 to 120 h), extracted, and analyzed using a validated high performance liquid chromatography tandem mass spectrometry assay. The study demonstrated the stability of both K and NK in whole blood up to 120 hours. These in vitro studies suggest that the concentrations of K and NK measured in the PK samples are reliable. The established stability results were successfully employed to investigate K and NK pharmacology studies in critically ill adults.
      PubDate: 2017-10-04T09:50:41.023925-05:
      DOI: 10.1002/bmc.4104
  • Chromatographic determination, decline dynamic, and risk assessment of
           sulfoxaflor in Asian pear and oriental melon
    • Authors: Md. Humayun Kabir; A.M. Abd El-Aty, Md. Musfiqur Rahman, Hyung Suk Chung, Han Sol Lee, Sung Woo Kim, Hee-Ra Chang, Ho-Chul Shin, Sung Shik Shin, Jae-Han Shim
      Abstract: The dissipation pattern of sulfoxaflor in Asian pear cultivated in an open field conditions and in oriental melon grown under plastic house conditions was each studied in two different locations. Residues in field-treated samples were determined using liquid chromatography (LC) coupled with an ultraviolet detector (UVD) and confirmed by liquid chromatography–tandem mass spectrometry (LC-MS/MS). A calibration curve for sulfoxaflor was linear over the concentration range 0.1–5.0 mg/L, with a coefficient of determination (R2 ≥) of 0.9999. The limits of detection (LOD) and quantification (LOQ) were 0.007 and 0.02 mg/kg, respectively. Recoveries at three fortification levels [LOQ, 10× LOQ, and maximum residue limit (MRL)] ranged from 70.5% to 86.2%, with a relative standard deviation (RSD) ≤5.8%. The dissipation half-lives were 10.8 and 7.9 days in pear and 5.4 and 5.9 days in oriental melon, at sites 1 and 2, respectively. Based on a pre-harvest residue limit (PHRL) curve, it was predicted that if the residues at 10 days before harvest in Asian pear are ˂0.54/0.61 mg/kg and those in oriental melon are ˂1.43/1.26 mg/kg, then the residue level would be below the MRL at harvest. Risk assessment at zero days showed a percentage accepted daily intake of 10.80% in Asian pear and 1.77% and 1.55% in oriental melon, for sites 1 and 2, respectively. These values indicate that the fruits are safe for consumption.
      PubDate: 2017-10-04T02:10:47.124585-05:
      DOI: 10.1002/bmc.4101
  • Bioassay, determination and separation of enantiomers of atenolol by
           direct and indirect approaches using liquid chromatography: A review
    • Authors: Sonika Batra; Ravi Bhushan
      Abstract: Atenolol, a β-adrenergic receptor antagonist, is a chiral compound used for the treatment of cardiovascular diseases and to treat hypertension, coronary heart disease, arrhythmias, sinus tachycardia and myocardial infarction, where it acts preferentially upon the β-adrenergic receptors in the heart. It is marketed as a racemate, but only (S)-enantiomer of (RS)-atenolol is responsible for the β-adrenoceptor blocking activity. Different chromatographic methods have been applied for separation and determination of enantiomers. In this article a review is presented on liquid chromatographic methods for enantioseparation of (RS)-atenolol by both direct and indirect approaches involving practical applications of several chiral stationary phases (CSPs), chiral derivatization reagents, and ligand exchange and impregnation methods. These include methods using both HPLC and TLC for separation, determination and bioassay of enantiomers of atenolol. Besides, some aspects of enantioseparation under achiral phases of liquid chromatography has been briefly mentioned as applicable to (RS)-atenolol. This review provides current available enantioseparation choices not only for (RS)-atenolol but for other applicable racemic drugs.
      PubDate: 2017-09-14T03:07:45.906884-05:
      DOI: 10.1002/bmc.4090
  • Chromatographic approaches for the characterization and quality control of
           therapeutic oligonucleotide impurities
    • Authors: N.M. El Zahar; N. Magdy, A.M. El-Kosasy, Michael G. Bartlett
      Abstract: Phosphorothioate (PS) oligonucleotides are a rapidly rising class of drugs with significant therapeutic applications. However, due to their complex structure and multi-step synthesis and purification processes, generation of low level impurities and degradation products are common. Therefore, they require significant investment in quality control and impurity identification. This requires the development of advanced methods for analysis, characterization and quantitation. In addition, the presence of the PS linkage leads to the formation of chiral centers which can affect their biological properties and therapeutic efficiency.In this review, the different types of oligonucleotide impurities and degradation products, with an emphasis on their origin, mechanism of formation and methods to reduce, prevent or even eliminate their production, will be extensively discussed. This review will focus mainly on the application of chromatographic techniques to determine these impurities but will also discuss other approaches such as mass spectrometry, capillary electrophoresis and nuclear magnetic resonance spectroscopy. Finally, the chirality and formation of diastereomer mixtures of PS oligonucleotides will be covered as well as approaches used for their characterization and the application for the development of stereochemically-controlled PS oligonucleotides.
      PubDate: 2017-09-04T06:01:06.901561-05:
      DOI: 10.1002/bmc.4088
  • Metabonomic analysis of serum reveals antifatigue effects of Yi Guan Jian
           on fatigue mice using Gas Chromatography coupled to Mass spectrometry
    • Authors: Sufang Shui; Xiaorong Cai, Rongqing Huang, Bingkun Xiao, Jianyun Yang
      Abstract: Yi Guan Jian (YGJ), one of the most commonly used traditional Chinese medicines (TCM), has been reported to possess significant antifatigue effects in the eastern. However, the mechanisms underlying its antifatigue effects remain largely unresolved. In this study, a metabonomics approach, involving gas chromatography coupled to mass spectrometry (GC/MS) and a multivariate statistical technique, was developed to estimate the extent to which YGJ alleviated the exhausting swimming induced fatigue of mice. High dose treatment with YGJ significantly extended the swimming time of fatigued mice. Significant alterations of metabolites involving amino acids, organic acids and carbohydrates were observed in the serum of fatigued mice, which was reversed by YGJ treatment while biochemical indexes returned to normal. These metabolic changes suggest that the antifatigue effect of YGJ is associated with the impairement of amino acid, organic acids and carbohydrates. It also appears that YGJ can induce significant metabolic alterations independent of the exhausting swimming induced metabolic changes. The significantly altered metabolites induced by YGJ intervention include L-2-Amino-acetoacetate, taurine, fumaric acid, malic acid, oxoadipic acid, L-Aspartate, all of which are associated with antifatigue properties. This suggests that YGJ exerts chemopreventive effects via antifatigue mechanisms.
      PubDate: 2017-09-03T19:45:20.469491-05:
      DOI: 10.1002/bmc.4085
  • Analytical methodologies for the stereoselective determination of
           fluoxetine: An overview
    • Authors: Gabriel Hancu; Melania Cârcu-Dobrin, Monica Budău, Aura Rusu
      Abstract: Fluoxetine is a widely used antidepressant belonging to the selective serotonin reuptake inhibitor class; it is used in the treatment of major depression, obsessive compulsive, premenstrual dysphoric, panic and post-traumatic stress disorders. Fluoxetine is an optical active pharmaceutical substance, which is used as a racemate in therapy, but stereospecific interactions associated with the serotonin-reuptake carrier, for both the parent drug and its active metabolite, norfluoxetine, have been described in the literature. Therefore, the stereoselective analysis of fluoxetine and norfluoxetine is important in order to characterize the pharmacokinetic and pharmacodynamic profile of the analytes. Several chromatographic and electrophoretic methods have been published in the literature for the chiral discrimination of fluoxetine enantiomers from different matrices. The purpose of the current review is to provide a systematic survey of the analytical techniques used for the chiral determination of fluoxetine and norfluoxetine covering a period of ~25 years.
      PubDate: 2017-07-26T21:45:32.310039-05:
      DOI: 10.1002/bmc.4040
  • A review of chromatographic methods for ketamine and its metabolites
           norketamine and dehydronorketamine
    • Authors: Eylem Funda Göktaş; Filiz Arıöz
      Abstract: Ketamine has a synthetic, sedative, nonbarbiturate and fast-acting anaesthetic 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. We have focused on sample pre-treatment and chromatographic techniques used since the year 2000 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 on the implementation of methods for studying ketamine and its metabolites in various research applications. It could be useful in forensic sciences including doping control and also in the therapeutic drug monitoring of ketamine and norketamine in human and animal clinical surgery.
      PubDate: 2017-07-11T21:50:35.521052-05:
      DOI: 10.1002/bmc.4014
  • Review of HPLC and LC–MS/MS assays for the determination of various
           nonsteroidal anti-androgens used in the treatment of prostate cancer
    • Authors: P.S. Suresh; Nuggehally R. Srinivas, Ramesh Mullangi
      Abstract: Prostate cancer is the most common cancer and one of the leading causes of cancer deaths in men. One of the commonly used approaches to treat metastatic prostate cancer was via first-generation nonsteroidal anti-androgens (NSAAs), namely flutamide, nilutamide, bicalutamide and topilutamide. Most prostate cancer patients who are initially responsive develop the most aggressive form of disease called castration-resistant prostate cancer. Second-generation NSAA receptor antagonists (enzalutamide, apalutamide and darolutamide) are emerging as additional new options to treat castration-resistant prostate cancer. The objective of this work was to review the literature on the bioanalytical methods for the quantification of first- and second-generation NSAA inhibitors in clinical (human plasma) and preclinical (mouse plasma, rat plasma, urine and tissue homogenates etc.) studies along with relevant case studies for some chosen drugs. Based on the review, it was concluded that the published methodologies using either HPLC or LC–MS/MS are well suited for the quantification of NSAA inhibitors in various biological fluids to delineate pharmacokinetic data.
      PubDate: 2017-07-11T20:50:30.253365-05:
      DOI: 10.1002/bmc.4034
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