Chiral bioanalysis of torcetrapib enantiomers in hamster plasma by normal-phase liquid chromatography and detection by atmospheric pressure chemical ionization tandem mass spectrometry.
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.
Department of Chemistry, JNTU College of Engineering, Kukatpally, Hyderabad 500072, India.
Ravi Kumar
RK
Trivedi
Buddhadev
B
Layek
T Santosh
TS
Kumar
Shivva
S
Vittal
Ramesh
R
Ganneboina
P K
PK
Dubey
Ramesh
R
Mullangi
Nuggehally R
NR
Srinivas
D000818:Animals; D000924:Anticholesteremic Agents / Q000097:blood* / Q000493:pharmacokinetics; D001274:Atmospheric Pressure; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D011804:Quinolines / Q000097:blood* / Q000493:pharmacokinetics; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000924:Anticholesteremic Agents; D011804:Quinolines; C483909:torcetrapib