Drug Metabolism and Disposition 2000-09-01

Synthesis and identification of the quaternary ammonium-linked glucuronide of 1-phenylimidazole in human liver microsomes and investigation of the human UDP-glucuronosyltransferases involved.

S C Vashishtha, E M Hawes, G McKay, D J McCann

Index: Drug Metab. Dispos. 28(9) , 1009-13, (2000)

Full Text: HTML

Abstract

1-Phenylimidazole was investigated as a potential model substrate with respect to formation of a quaternary ammonium-linked glucuronide (N(+)-glucuronide) at an aromatic type tertiary amine. A reference sample of the potential N(+)-glucuronide metabolite of 1-phenylimidazole was obtained by organic synthesis. The structural identity of the metabolite formed by incubation of 1-phenylimidazole with human liver microsomes was proven to be the N(+)-glucuronide by exhibiting the same HPLC retention time and electrospray ionization mass spectrum as the reference sample. The screening of 1-phenylimidazole against a panel of nine expressed human UDP-glucuronosyltransferases indicated the involvement of UGT1A3 and UGT1A4 in the formation of the N(+)-glucuronide metabolite.