title: Stereoselective degradation of chiral fungicide myclobutanil in rat liver microsomes.
abstract: Myclobutanil, (RS)-2-(4-chlorophenyl)-2-(1H-1, 2, 4-triazol-1-ylmethyl)hexanenitrile is a broad-spectrum systemic triazole fungicide which consists of a pair of enantiomers. The stereoselective degradation of myclobutanil was investigated in rat liver microsomes. The concentrations of myclobutanil enantiomers were determined by high-performance liquid chromatography (HPLC) with a cellulose-tris-(3,5-dimethyl-phenylcarbamate)-based chiral stationary phase (CDMPC-CSP) under reversed phase condition. The t(1/2) of (+)-myclobutanil is 8.49 min, while the t(1/2) of (-)-myclobutanil is 96.27 min. Such consequences clearly indicated that the degradation of myclobutanil in rat liver microsomes was stereoselective and the degradation rate of (+)-myclobutanil was much faster than (-)-myclobutanil. In addition, significant differences between two enantiomers were also observed in enzyme kinetic parameters. The V(max) of (+)-myclobutanil was about 4-fold of (-)-myclobutanil and the CL(int) of (+)-myclobutanil was three times as much as (-)-myclobutanil after incubation in rat liver microsomes. Corresponding consequences may shed light on the environmental and ecological risk assessment for myclobutanil and may improve human health.
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Wentao
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000818:Animals; D005659:Fungicides, Industrial; D006801:Humans; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry* / Q000378:metabolism; D009570:Nitriles / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013997:Time Factors; D014230:Triazoles / Q000737:chemistry* / Q000378:metabolism
chemical_list: D005659:Fungicides, Industrial; D009570:Nitriles; D014230:Triazoles; C446685:systhane
keywords: myclobutanil; rat; rat liver microsomes; stereoselective degradation