RT Journal Article
SR Electronic
T1 Synthesis and Identification of the Quaternary Ammonium-Linked Glucuronide of 1-Phenylimidazole in Human Liver Microsomes and Investigation of the Human UDP-Glucuronosyltransferases Involved
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1009
OP 1013
VO 28
IS 9
A1 Vashishtha, Sarvesh C.
A1 Hawes, Edward M.
A1 McKay, Gordon
A1 McCann, Denis J.
YR 2000
UL http://dmd.aspetjournals.org/content/28/9/1009.abstract
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