title: Evaluating the enantioselective degradation and novel metabolites following a single oral dose of metalaxyl in mice.
abstract: Metalaxyl [N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-D,L-alaninemethylester] is a systemic fungicide widely used in agriculture. In this study, the enantioselective distribution, degradation and excretion of metalaxyl were investigated after oral gavage administration of rac-metalaxyl to mice. Concentration of metalaxyl and its enantiomers was determined by HPLC-MS/MS. The results showed that R-metalaxyl was much higher than S-metalaxyl in heart, liver, lung, urine and feces. As for the strong first pass effect, concentrations of metalaxyl in liver were much higher than those in other tissues. The total body clearance (CL) of metalaxyl in mice was 1.77 L h(-1 )kg(-1) and degradation half-lives of (t1/2) of S-metalaxyl and R-metalaxyl in liver were 2.2 h and 3.0 h, respectively. Such results indicated the enantioselectivity of metalaxyl lies in distribution, degradation and excretion processes in mice. Main metabolites were also determined and biotransformation reactions were hydroxylation, demethylation and didemethylation. Furthermore, metabolite concentrations in urine and feces were much higher than those in tissues. These results may have potential implications to predict toxicity and provide additional information associated with adverse health effects for risk assessment of metalaxyl.
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Institute of Quality Standards & Testing Technology for Agro-Products, Key Laboratory of Agro-Product Quality and Safety, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
authors.forename: Dezhen
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing 100193, China. Electronic address: zqzhou@cau.edu.cn.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000284:Administration, Oral; D000409:Alanine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D000818:Animals; D002853:Chromatography, Liquid; D005243:Feces / Q000737:chemistry; D005659:Fungicides, Industrial / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000652:urine; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
chemical_list: D005659:Fungicides, Industrial; C028175:metalaxyl; D000409:Alanine
keywords: Degradation; Enantioselectivity; Metabolite; Metalaxyl; Mice