title: Stereoselective degradation of metalaxyl and its enantiomers in rat and rabbit hepatic microsomes in vitro.
abstract: The stereoselective degradations of racemate metalaxyl (rac-MX) and its single enantiomers in rat and rabbit hepatic microsomes were assayed by a chiral high-performance liquid chromatography method.        The t(1/2) of (+)-S-MX in rat liver microsomes was between 7-8 min tested by rac-MX and the individual (+)-S-enantiomer, respectively, and that for (-)-R-MX was 15-16 min. In contrast, t(1/2) in rabbit liver microsomes was much longer and showed great difference when using racemate and single enantiomer, which was similar to the results of in vivo study.        The enantioselectivity in rat hepatic microsomes was more evident and the degradations of MX enantiomers in rat and rabbit hepatic microsomes were Nicotinamide adenine dinucleotide phosphate-dependent.        Michaelis constant (K(m)) and intrinsic metabolic clearance (CL(int)) of (+)-S-MX were larger than that of (-)-R-MX and there was no chiral inversion from (+)-S-MX to (-)-R-MX or vice versa in both rat and rabbit hepatic microsomes.
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Shen
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Xu
authors.forename: Wentao
authors.initials: W
authors.lastname: Zhu
authors.forename: Ziheng
authors.initials: Z
authors.lastname: Dang
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Donghui
authors.initials: D
authors.lastname: Liu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005659:Fungicides, Industrial / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D005659:Fungicides, Industrial; C028175:metalaxyl; D009249:NADP; D000409:Alanine