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dc.contributor.authorJu, Wujian
dc.contributor.authorYang, Sihyung
dc.contributor.authorSun, H.
dc.contributor.authorSampson, M.
dc.contributor.authorWang, Michael Zhuo
dc.identifier.citationJu W, Peng K, Yang S, Sun H, Sampson M and Wang MZ. A Chiral HPLC-MS/MS Method for Simultaneous Quantification of Warfarin Enantiomers and its Major Hydroxylation Metabolites of CYP2C9 and CYP3A4 in Human Plasma. Austin J Anal Pharm Chem. 2014;1(2): 1010. ISSN:2381-8913en_US
dc.description.abstractWarfarin is an oral anticoagulant that requires frequent therapeutic drug monitoring due to a narrow therapeutic window, considerable interindividual variability in drug response, and susceptibility to drug-drug and drug-diet interactions. Enantiomeric separation and quantification of warfarin enantiomers and clinically important major hydroxylation metabolites are essential for drug interaction studies and phenotypic characterization of CYP2C9 and CYP3A4, the major Cytochrome P450 (CYP) enzymes involved in warfarin metabolism. Here, we describe the development and validation of a chiral high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)-based quantification of R-warfarin, S-warfarin, S-7-hydroxywarfarin (the major CYP2C9metabolite) and (9R; 10S)-10-hydroxywarfarin (the CYP3A4 metabolite) in human plasma. Simple protein precipitation-based extraction showed good recovery of analytes (82.9 - 96.9%). The developed method exhibited satisfactory intra-day and inter-day accuracy and precision. The lower limits of detection were 0.25nM (or ~0.08 ng/ml) for the warfarin enantiomers and 0.1nM (or ~0.04 ng/mL) for S-7-hydroxywarfarinand (9R; 10S)-10-hydroxywarfarin using only 50μL plasma during extraction. The validated method was successfully applied to analyze plasma samples obtained from a healthy human subject who enrolled in a clinical drug interaction study involving warfarin.en_US
dc.publisherAustin Publishing Groupen_US
dc.subjectChiral separationen_US
dc.subjectProtein precipitation extractionen_US
dc.titleA chiral HPLC-MS/MS method for simultaneous quantification of warfarin enantiomers and its major hydroxylation metabolites of CYP2C9 and CYP3A4 in human plasmaen_US
kusw.kuauthorJu, Wujian
kusw.kuauthorYang, Sihyung
kusw.kuauthorWang, Michael Zhuo
kusw.kudepartmentPharmaceutical Chemistryen_US
dcterms.rightsThis is an open access article under the terms of the Attribution 4.0 International (CC BY 4.0).
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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