Cytochrome P450 (CYP) 2C9 and CYP2C19 genetic mutant could influence the plasma concentration of glipizide in human subjects, which refers to glipizide safety and adverse effects in clinic practice. A further study to investigate the relationship of the concentrations between glipizide and its metabolites in human with different CYP mutants was valuable. We firstly develop a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of glipizide and its hydroxylated metabolites in human urine. After simple protein precipitation with methanol including 4'-OH-tolbutamide and gliclazide (both are internal standards), the analytes were chromatographed on a reversed-phased column with a mobile phase of 0.1% formic acid in acetonitrile and 0.1% formic acid in water by a gradient elution. The ion transitions of the precursor to the product ion were principally protonated ions [M + H](+) at m/z 446.4 -> m/z 321.1 for glipizide, m/z 462.2 -> m/z 321.1 for the four hydroxylated forms of glipizide, m/z 287.2 -> m/z 188.0 for 4'-OH-tolbutami de, and m/z 324.1 -> m/z 127.1 for gliclazide. The method was linear over a concentration range of 0.02-20.0 ng/mL. The intraday and inter-day variances were less than 9.9%, and accuracy was within +/- 6.8%. The method was successfully applied to the urinary phenotyping study in volunteers after a single oral administration of 5-mg glipizide tablet, and two new hydroxycyclohexyl metabolites of glipizide (OH-gp), 4-cis-OH-gp and 3-trans-OH-gp, were found in this study. (C) 2017 Elsevier B.V. All rights reserved.
[1]Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Clin Pharmacokinet Lab, 528 Zhanghent Rd, Shanghai 201203, Peoples R China.
[2]Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Dept Clin Pharmacol, 528 Zhanghent Rd, Shanghai 201203, Peoples R China.
[3]Shanghai Univ Tradit Chinese Med, Baxic Med Coll, Dept Febile Dis, Shanghai 201203, Peoples R China.
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