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

1-Phenylimidazole was investigated as a potential model substrate with resp ect to formation of a quaternary ammonium-linked glucuronide (N+-glucuronid e) at an aromatic type tertiary amine. A reference sample of the potential N+-glucuronide metabolite of 1-phenylimidazole was obtained by organic synt hesis. The structural identity of the metabolite formed by incubation of 1- phenylimidazole with human liver microsomes was proven to be the N+-glucuro nide 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 indica ted the involvement of UGT1A3 and UGT1A4 in the formation of the N+-glucuro nide metabolite.