Investigation And Application Of Quantitative Analytical Methods Of Rosiglitazone And Glyburide In Plasma

1. Determination of rosiglitazone in plasma by LC/MS/MSAim: A sensitive and selective liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for the determination of rosiglitazone in human plasma was developed. Methods: The analytes were extracted from plasma samples by liquid-liquid extraction, then chromatographed by using a Zorbax SB-C₁₈ column. The mobile phase consisted of acetonitrile-water-formic acid (90 :10 : 0.5 , v/v/v). A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor → product ion combinations of m/z 358 → 135 and m/z 256 → 167 was performed. Results: The linear calibration curve was obtained in the concentration range of 0.50 - 1000 ng/mL. The method was applicated to study the pharmacokinetics of 20 healthy volunteers after oral administration of 4 mg of rosiglitazone. Conclution: The method is proved to be sensitive, rapid and robust, and suitable for clinical pharmacokinetic investigations of rosiglitazone.2. Determination of glyburide in plasma by LC/MS/MSAim: A rapid and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for determination of glyburide in human plasma. Methods: The analytes were extracted from plasma samples by liquid-liquid extraction, then chromatographed by a Zorbax SB-C₈ column. The mobile phase consisted of acetonitrile-water-formic acid (90 :10 :0.2, v/v/v). A tandem mass spectrometer equipped with atmospheric pressure chemical ionization source was used as detector and operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor → product ion combinations of m/z 494 → 369 and m/z 324→ 127 was used to quantify glyburide and the internal standard, respectively. Results: The linear calibration curve was obtained in the concentration range of 0.50 - 500 ng/mL. The method was successfully applied for the evaluation of the pharmacokinetics of glyburide in 20 volunteers after...