The enantioselective metabolic mechanism of quizalofop-ethyl and quizalofop-acid enantiomers in animal: protein binding, intestinal absorption, and in vitro metabolism in plasma and the microsome

RSC Advances Pub Date: 2016-10-07 DOI: 10.1039/C6RA19391A

Abstract

To investigate the metabolic mechanism and enantioselectivity of the chiral herbicide quizalofop-ethyl and its primary chiral metabolite quizalofop-acid in animals by oral administration, the effects of the processes involved in digestion, absorption, transportation and metabolism, such as protein binding (pepsin, trypsin and serum albumin), intestinal absorption (everted gut sac), and degradation (plasma, liver microsome and cytosol) were studied in vitro. Protein binding experiments showed that quizalofop-ethyl interacted with pepsin, trypsin and serum albumin without enantioselectivity and the proteins did not stimulate metabolic processes that would produce quizalofop-acid. In the everted gut sac, quizalofop-ethyl was degraded rapidly to quizalofop-acid without enantioselectivity and the preferential absorption of (+)-quizalofop-acid was observed throughout the gut. In plasma, the metabolic process of quizalofop-ethyl was enantioselective with preferential degradation of (+)-quizalofop-ethyl and generation of (+)-quizalofop-acid. However there was no enantioselectivity in the degradation of quizalofop-ethyl or formation of quizalofop-acid in liver microsome. The metabolism of quizalofop-acid was nonenantioselective by liver microsome, sulfotransferase and glucuronosyltransferase. It could be inferred that the enzymes present in the lumen of intestine, blood and liver might facilitate the rapid transformation of quizalofop-ethyl to quizalofop-acid after oral administration, and the enantioselective absorption of quizalofop-acid enantiomers by intestine was the main reason for the enantioselectivity observed in rats in vivo.

Graphical abstract: The enantioselective metabolic mechanism of quizalofop-ethyl and quizalofop-acid enantiomers in animal: protein binding, intestinal absorption, and in vitro metabolism in plasma and the microsome
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