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Development and validation of an enantioselective LC‐MS/MS method to quantify enantiomers of (±)‐TAK‐700 in rat plasma: lack of in vivo inversion of (+)‐TAK‐700 (Orteronel) to its antipode
Author(s) -
Gurav Sandip,
Police Anitha,
Zainuddin Mohd,
Punde Ravindra Ramachandra,
Dewang Purushottam,
V Chandregowda,
Kethiri Raghava Reddy,
Rajagopal Sriram,
Mullangi Ramesh
Publication year - 2013
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.2764
Subject(s) - chemistry , chromatography , enantiomer , phenacetin , stereoselectivity , ammonium acetate , in vivo , pharmacokinetics , selected reaction monitoring , elution , enantioselective synthesis , methanol , tandem mass spectrometry , high performance liquid chromatography , mass spectrometry , stereochemistry , pharmacology , organic chemistry , medicine , biology , catalysis , microbiology and biotechnology
A highly sensitive, specific and enantioselective assay has been developed and validated for the estimation of TAK‐700 enantiomers [(+)‐TAK‐700 and (−)‐TAK‐700] in rat plasma on LC‐MS/MS‐ESI in the positive‐ion mode. Liquid–liquid extraction was used to extract (±)‐TAK‐700 enantiomers and IS (phenacetin) from rat plasma. TAK‐700 enantiomers were separated using methanol and 5 m m ammonium acetate (80:20, v/v) at a flow rate of 0.7 mL/min on a Chiralcel OJ‐RH column. The total run time was 7.0 min and the elution of (+)‐TAK‐700, (−)‐TAK‐700 and IS occurred at 3.71, 4.45 and 4.33 min, respectively. The MS/MS ion transitions monitored were m/z 308.2 → 95.0 for TAK‐700 and m/z 180.2 → 110.1 for IS. The standard curves for TAK‐700 enantiomers were linear ( r 2 > 0.998) in the concentration range 2.01–2015 ng/mL for each enantiomer. The inter‐ and intra‐day precisions were in the ranges 3.74–7.61 and 2.06–8.71% and 3.59–9.00 and 2.32–11.0% for (+)‐TAK‐700 and (−)‐TAK‐700, respectively. Both the enantiomers were found to be stable in a battery of stability studies. This novel method was applied to the study of stereoselective oral pharmacokinetics of (+)‐TAK‐700 and it was unequivocally demonstrated that (+)‐TAK‐700 does not undergo chiral inversion to its antipode in vivo . Copyright © 2012 John Wiley & Sons, Ltd.