title: Simultaneous and stereospecific analysis of warfarin oxidative metabolism using 2D LC/Q-TOF.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Life Science Center, Agilent Technologies, Inc., Bangalore 560048, India.
authors.forename: Siji
authors.initials: S
authors.lastname: Joseph
authors.affiliation: Pharmaceutical Candidate Optimization, Biocon Bristol-Myers Squibb Research & Development Center, Syngene International Limited, Bangalore 560100, India.
authors.forename: Murali
authors.initials: M
authors.lastname: Subramanian
authors.affiliation: Life Science Group, Agilent Technologies, Inc., Santa Clara, CA 95080, USA.
authors.forename: Smriti
authors.initials: S
authors.lastname: Khera