Differences and Similarities in the Metabolism of Glyburide for Various Species: An Analysis by LC-DAD-Q-TRAP-MS/MS

Abstract

Studies were conducted on the Metabolism of sulfonylurea drug glyburide (5-chloro-N-(4-[N-(cyclohexylcarbamoyl) sulfamoyl] phenethyl)-2-methoxybenzamide) in human, mouse, rat, dog and monkey hepatic microsomes. Liquid chromatography with Diode array detector (LC-DAD) hyphenated with Q-Trap-Mass Spectrometer (Q-TRAP-MS/ MS) was employed to study the metabolism of glyburide in different species. The primary objective of the present study is to identify the similarities and differences in the metabolism of glyburide and to confirm the recent newly identified metabolites across the species. Results obtained from LC-UV and LC-MS/MS confirm the similarities and differences in the biotransformation of glyburide across the species. LC-UV-MS/MS data clearly suggests that the quantities of metabolites formed in all the species are dissimilar. Drug metabolite ratio is also different in all the species considered for tests. Mono-oxygenated metabolites and a metabolite due to the ring loss were identified in all the species. Similarities and differences in the metabolism of glyburide confirm the role of cytochrome P450 (CYP 45) enzymes and its distinct activity across the species.