Chiral bioanalysis of torcetrapib enantiomers in hamster plasma by normal-phase liquid chromatography and detection by atmospheric pressure chemical ionization tandem mass spectrometry

Ravi Kumar Trivedi, Buddhadev Layek, T. Santosh Kumar, Shivva Vittal, Ramesh Ganneboina, P. K. Dubey, Ramesh Mullangi, Nuggehally R. Srinivas

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6 Scopus citations

Abstract

A highly sensitive and enantioselective assay has been developed and validated for the estimation of torcetrapib (TTB) enantiomers [(+)-TTB and (-)-TTB] in hamster plasma with chiral liquid chromatography coupled to tandem mass spectrometry with an atmospheric pressure chemical ionization interface in the negative-ion mode. The assay procedure involves liquid-liquid extraction of TTB enantiomers and IS (DRL-16126) from 100 μL hamster plasma with acetonitrile. TTB enantiomers were separated using n-hexane:propanol (80:20, v/v) at a flow rate of 0.7 mL/min on a Chiralpak AD column. The MS/MS ion transitions monitored were 599.2 → 340.2 for TTB and 623.2 → 298.1 for IS. Absolute recovery was found to be between 64 and 68% for TTB enantiomers and >100% for IS. The standard curves for TTB enantiomers were linear (r2 > 0.995) in the concentration range 5-2500 ng/mL for each enantiomer with an LLOQ of 5 ng/mL for each enantiomer. The inter- and intra-day precisions were in the range of 10.5-12.4 and 9.15-11.5% and 3.75-12.9 and 5.16-12.5% for (+)-TTB and (-)-TTB, respectively. Accuracy in the measurement of quality control (QC) samples was in the range 91.3-105 and 88.6-111% for (+)-TTB and (-)-TTB, respectively. This novel method has been applied to the study of stereoselective oral pharmacokinetics of (-)-TTB.

Original languageEnglish (US)
Pages (from-to)227-234
Number of pages8
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume860
Issue number2
DOIs
StatePublished - Dec 15 2007

Keywords

  • APCI
  • Chiralpak AD
  • Enantioselective
  • LC-MS/MS
  • Pharmacokinetics
  • Plasma
  • Torcetrapib
  • Validation

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