Simultaneous and stereospecific analysis of warfarin oxidative metabolism using 2D LC/Q-TOF

Warfarin is a widely used racemic anticoagulant with narrow therapeutic range and wide interindividual response to treatment. This is due to the extensive and differential clearance of R- and S-warfarin with the involvement of several polymorphic CYP450 enzymes resulting in the formation of several...

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Bibliographic Details
Published inBioanalysis Vol. 7; no. 18; pp. 2297 - 2309
Main Authors Joseph, Siji, Subramanian, Murali, Khera, Smriti
Format Journal Article
LanguageEnglish
Published England 01.09.2015
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Summary:Warfarin is a widely used racemic anticoagulant with narrow therapeutic range and wide interindividual response to treatment. This is due to the extensive and differential clearance of R- and S-warfarin with the involvement of several polymorphic CYP450 enzymes resulting in the formation of several stereoisomeric oxidative metabolites. A stereospecific 2DLC/Q-TOF method was developed for the simultaneous identification and quantitation of hydroxylated warfarin metabolites from a single sample analysis. Using this method metabolites from rat microsomal and plated hepatocyte incubations with R-, S- and (R/S)-warfarin were estimated. Multiheart cutting with high resolution MS and MS/MS analysis is suggested as a viable approach for achiral-chiral separation of metabolites of warfarin and other chiral or prochiral drugs.
ISSN:1757-6180
1757-6199
DOI:10.4155/bio.15.119