Abstract
Metabolites of unlabeled and pyrazole-3-14C-labeled tebufenpyrad, N-(4-tert-butylbenzyl)-4-chloro-3-ethyl-1-methylpyrazole-5-carboxamide, formed in the in vitro system using 9000×g supernatant of rat liver homogenate and in vivo system of rats were identified. In the in vitro system, the major metabolites were N-(4-tert-butylbenzyl)-4-chloro-3-(1-hydroxyethyl)-1-methylpyrazole-5-carboxamide [designated as OH-M] formed by hydroxylation [I] of the ω-1 position of the ethyl group and N-[4-(1-carboxy-1-methylethyl) benzyl]-4-chloro-3-ethyl-1-methylpyrazole-5-carboxamide [M-CA] formed by oxidation [II] of the methyl group in the tert-butyl moiety to the carboxyl group. In the in vivo system, the major metabolite was N-[4-(1-carboxy-1-methylethyl) benzyl]-4-chloro-3-(1-hydroxyethyl)-1-methylpyrazole-5-carboxamide [OH-M-CA] (30.9% of dose), which was formed by combined reactions of [I] and [II], and mainly excreted in urine. The other significant metabolites were [M-CA] (6.2%) and two sulfate esters of N-[4-(1-hydroxymethyl-1-methylethyl) benzyl]-4-chloro-3-(1-hydroxyethyl)-1-methylpyrazole-5-carboxamide conjugated at the hydroxymethyl group in the tert-butyl moiety [OH-M-OSO3H] (5.7%) and the 1-hydroxyethyl group on the pyrazole ring [HO3SO-M-OH] (7.0%), which were mainly excreted in feces. A large number of minor metabolites were formed by N-demethylation, oxidation at the ω-1 position of the ethyl group to the ketone, and hydroxylation and carboxylation at the ω position of the ethyl group. However, cleavage of the amide or the benzyl methylene carbon-nitrogen bond was limited.
