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Joseph S, Subramanian M, Khera S. Simultaneous and stereospecific analysis of warfarin oxidative metabolism using 2D LC/Q-TOF. Bioanalysis. 2015;7(18):2297-2309doi: 10.4155/bio.15.119.
Joseph, S., Subramanian, M., & Khera, S. (2015). Simultaneous and stereospecific analysis of warfarin oxidative metabolism using 2D LC/Q-TOF. Bioanalysis, 7(18), 2297-2309. https://doi.org/10.4155/bio.15.119
Joseph, Siji, et al. "Simultaneous and stereospecific analysis of warfarin oxidative metabolism using 2D LC/Q-TOF." Bioanalysis vol. 7,18 (2015): 2297-2309. doi: https://doi.org/10.4155/bio.15.119
Joseph S, Subramanian M, Khera S. Simultaneous and stereospecific analysis of warfarin oxidative metabolism using 2D LC/Q-TOF. Bioanalysis. 2015 Sep;7(18):2297-2309. doi: 10.4155/bio.15.119. Epub 2015 Jun 24. PMID: 26105112.
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Bioanalysis. 2015 Sep;7(18):2297-2309. doi: 10.4155/bio.15.119. Epub 2015 Jun 24.

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

Bioanalysis

Siji Joseph, Murali Subramanian, Smriti Khera

Affiliations

  1. Life Science Center, Agilent Technologies, Inc., Bangalore 560048, India.
  2. Pharmaceutical Candidate Optimization, Biocon Bristol-Myers Squibb Research & Development Center, Syngene International Limited, Bangalore 560100, India.
  3. Life Science Group, Agilent Technologies, Inc., Santa Clara, CA 95080, USA.

PMID: 26105112 DOI: 10.4155/bio.15.119

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.

CONCLUSION: 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.

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