title: Rapid metabolite discovery, identification, and accurate comparison of the stereoselective metabolism of metalaxyl in rat hepatic microsomes.
abstract: Metabolite identification and quantitation impose great challenges on risk assessment of agrochemicals, as many metabolite standards are generally unavailable. In this study, metalaxyl metabolites were identified by time-of-flight mass spectrometry and semiquantified by triple quadrupole tandem mass spectrometry with self-prepared (13)C-labeled metalaxyl metabolites as internal standards. Such methodology was employed to characterize the stereoselective metabolism of metalaxyl in rat hepatic microsomes successfully. Metabolites derived from hydroxylation, demethylation, and didemethylation were identified and semiquantified. The results indicated that (+)-S-metalaxyl eliminated preferentially as the enantiomer fraction was 0.32 after 60 min incubation. The amounts of hydroxymetalaxyl and demethylmetalaxyl derived from (-)-R-metalaxyl were 1.76 and 1.82 times higher than that of (+)-S-metalaxyl, whereas didemethylmetalaxyl derived from (+)-S-metalaxyl was 1.44 times larger than that from (-)-R-metalaxyl. This study highlights a new quantitation approach for stereoselective metabolism of chiral agrochemicals and provides more knowledge on metalaxyl risk assessment.
authors.affiliation: Department of Applied Chemistry, China Agricultural University , Beijing 100193, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Qiu
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
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: D016573:Agrochemicals; D000409:Alanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002247:Carbon Isotopes; D005659:Fungicides, Industrial; D006900:Hydroxylation; D008297:Male; D013058:Mass Spectrometry; D008745:Methylation; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
chemical_list: D016573:Agrochemicals; D002247:Carbon Isotopes; D005659:Fungicides, Industrial; C028175:metalaxyl; D000409:Alanine
keywords: LC-MS; metabolic profile; metabolite identification; rat hepatic microsome; stereoselective metabolism