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

Abstract

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.

Sensitivity of Liver Injury in Heterozygous Sod2 Knockout Mice Treated with Troglitazone or Acetaminophen

“…The amorphous coprecipitate of troglitazone was suspended in 0.5% carboxymethylcellulose sodium solution (10 mL/kg body weight of 3% troglitazone suspension was given) for oral administration of 300 mg/kg of troglitazone once a day for twenty-eight days. According to New et al (2007), plasma level (C max ) in mice after a single intraperitoneal administration of 30 mg/kg troglitazone was 9.8 mg/L. On the other hand, it was reported that C max after a single oral administration of 50 mg/kg and 400 mg/kg troglitazone was 8.78 mg/L and 23.3 mg/L, respectively (Herman et al 2002).…”

“…According to New et al (2007), plasma level (C max ) in mice after a single intraperitoneal administration of 30 mg/kg troglitazone was 9.8 mg/L. On the other hand, it was reported that C max after a single oral administration of 50 mg/kg and 400 mg/kg troglitazone was 8.78 mg/L and 23.3 mg/L, respectively (Herman et al 2002).…”

Development and validation of a UPLC–MS/MS method for quantification of SKLB010, an investigational anti-inflammatory compound, and its application to pharmacokinetic studies in beagle dogs

“…Therefore, the optimization of mobile phase components was critical. Several mobile phases have been reported for the separation of thiazolidinediones on C18 column, such as methanol-water [16], acetonitrile-formic acid-water [17], acetonitrile-ammonium acetate-TFA-water [18], and acetonitrile-ammonium acetate-water [19]. In this work we have trialed different mobile phase combinations to achieve good resolution and symmetric peak shapes for the analyte and I.S., as well as a short run time.…”

The Sod2 mutant mouse as a model for oxidative stress: A functional proteomics perspective

“…To achieve realistic systemic exposure of troglitazone similar to humans, we first ascertained using plasma ultra-performance liquid chromatography coupled to QTRAP MS that doses given to Sod2 þ/À mice resulted in plasma concentrations comparable to humans (New et al, 2007). Next we performed a time-course proteomics study and found a total of 70 proteins that were differentially expressed, 24 from the 2 weeks dosing regime and 46 from the 4 weeks dosing regime.…”