A Simplified and Highly Sensitive Method for the Quantification of Glipizide by LC-MS/MS and its Application to a Pharmacokinetic Study in Healthy Chinese Volunteers

A simplified and highly sensitive high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS) method was described in this study for the determination of glipizide in human plasma employing glimepiride as the internal standard (IS). Sample preparation was accomplished through one-step protein precipitation with acetonitrile, and chromatographic separation was achieved on a Hedera ODS-2 column (2.1 x 150 mm, 5 mu m) maintained at 30 degrees C using a mobile phase of acetonitrile and ammonium acetate 10 mM buffer containing 0.2% formic acid (55:45, v/v). Mass spectrometric analysis was performed using an API 4000 triple quadrupole mass spectrometer coupled with an electrospray ionization source in positive ion mode. The multiple reaction monitoring (MRM) mode of precursor-product ion transition at m/z 446.1 -> 321.1 and m/z 491.1 -> 352.1 was respectively utilized to quantify glipizide and IS. The method was proved to be precise and accurate at linearity concentration range of 3.164-843.8 ng/mL with correlation coefficients of more than 0.9990 for glipizide. The lower limit of quantification (LLOQ) was 3.164 ng/mL. No matrix effect and carryover effect were observed for the analyte. The validated method was successfully applied to investigate the pharmacokinetic profile of glipizide in healthy Chinese subjects following single oral administration of glipizide controlled-release tablets (GCRT).