Torcetrapib
Chiral LC-MS/MS assay separates torcetrapib enantiomers in hamster plasma down to 5 ng/mL (J Chromatogr B 2007)
Original title: Chiral bioanalysis of torcetrapib enantiomers in hamster plasma by normal-phase liquid chromatography and detection by atmospheric pressure chemical ionization tandem mass spectrometry
Researchers developed and validated a chiral liquid chromatography-tandem mass spectrometry assay to separately quantify the (+) and (-) enantiomers of torcetrapib (TTB) in hamster plasma, using a Chiralpak AD column with an n-hexane:propanol mobile phase and atmospheric pressure chemical ionization in negative-ion mode. Absolute recovery was 64% to 68% for the TTB enantiomers, and standard curves were linear (r2 >0.995) from 5 to 2500 ng/mL with a lower limit of quantitation of 5 ng/mL for each enantiomer. Inter- and intra-day precision ranged from 3.75% to 12.9% and accuracy from 88.6% to 111% for the two enantiomers. The authors applied this novel method to study the stereoselective oral pharmacokinetics of the (-)-TTB enantiomer.
Original 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 microL 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 (r(2)>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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.