Pharmacokinetic study of intraperitoneally administered troglitazone in mice using ultra-performance liquid chromatography/tandem mass spectrometry

A rapid and sensitive ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method was developed and validated for the determination of troglitazone in mouse plasma. Troglitazone and its internal standard (IS), rosiglitazone, were separated on an ACQUITY UPLC BEH C(18) column (1.7 microm particle size, 50 x 2.1 mm i.d.) by gradient elution with water and methanol at a flow rate of 0.5 mL/min. The cycle time of each analysis was 2.5 min. Rosiglitazone and troglitazone eluted at 1.13 and 1.57 min, respectively, and were chromatographically resolved from the ion suppression and enhancement zones due to the biological matrix effect. Quantitation of the analytes was performed in electrospray negative ionization mode (ESI -ve) using multiple reaction monitoring (MRM) experiments. The weighted (1/x) calibration curve was quadratic over the plasma concentration range 1-2500 ng/mL with a correlation coefficient (r(2)) of 0.9966. The limit of quantitation (LOQ) of troglitazone in mouse plasma was lower than 1 ng/mL. The inter- and intra-day variations of the assay were lower than 12.1%; the overall accuracy ranged from 86.4-110.2% and recovery from spiked plasma was more than 60%. The developed method was successfully applied to determine troglitazone in mouse plasma after intraperitoneal administration.