PT  - JOURNAL ARTICLE
AU  - Vashishtha, Sarvesh C.
AU  - Hawes, Edward M.
AU  - McKay, Gordon
AU  - McCann, Denis J.
TI  - Synthesis and Identification of the Quaternary Ammonium-Linked Glucuronide of 1-Phenylimidazole in Human Liver Microsomes and Investigation of the Human UDP-Glucuronosyltransferases Involved
DP  - 2000 Sep 01
TA  - Drug Metabolism and Disposition
PG  - 1009--1013
VI  - 28
IP  - 9
4099  - http://dmd.aspetjournals.org/content/28/9/1009.short
4100  - http://dmd.aspetjournals.org/content/28/9/1009.full
SO  - Drug Metab Dispos2000 Sep 01; 28
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics