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. (19th June 2012)

• Record Type: Journal Article
• Authors: Gurav, Sandip; Police, Anitha; Zainuddin, Mohd; Punde, Ravindra Ramachandra; Dewang, Purushottam; V, Chandregowda; Kethiri, Raghava Reddy; Rajagopal, Sriram; Mullangi, Ramesh
• Is Part Of: Biomedical chromatography. Volume 27:Number 2(2013:Feb.)
• Page Start: 164
• Page End: 171
• Publication Date: 2012-06-19
• Subjects: Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.2764
• Languages: English
• ISSNs: 0269-3879

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>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<sc>m</sc> 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 <italic>m/z</italic> 308.2 → 95.0 for TAK‐700 and <italic>m/z</italic> 180.2 → 110.1 for IS. The standard curves for TAK‐700 enantiomers were linear (<italic>r</italic>² &gt; 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 <italic>in vivo</italic>. Copyright © 2012 John Wiley &amp; Sons, Ltd.</p> </abstract>