Metabolism of mequindox in liver microsomes of rats, chicken and pigs

摘要

Mequindox, 3-methyl-2-quinoxalinacetyl-1,4-dioxide, is a quinoxaline-N,N-dioxide used in veter-inary medicine as a antibacterial in China. To gain an understanding of the interspecies differencesin the metabolism of mequindox, comparative metabolite profiles were qualitatively and quanti-tatively carried out for the first time in rat, chicken and pig liver microsomes by high-performanceliquid chromatography combined with hybrid ion trap/time-of-flight mass spectrometry. A total of 14metabolites were characterized based on their accurate MS~2spectra and known structure ofmequindox. The in vitro metabolic pathways of mequindox in three species were proposed asN Ogroup reduction, carbonyl reduction, N—Ogroup reduction followed by carbonyl ormethyl mono-hydroxylation. A metabolic pathway involving N→O group reduction followed byacetyl group mono-hydroxylation in only chicken was also proposed. There was also quantitativespecies difference for mequindox metabolism in three species. 1-Desoxymequindox was the mainmetabolite in all species, but otherwise there were some qualitative interspecies differences inmequindox major metabolites. This work has revealed biotransformation characteristics of mequin-dox among different species, and moreover will further facilitate the explanations of the biologicalactivities of mequindox in animals.