title: Enantioselective degradation of hexaconazole in rat hepatic microsomes in vitro.
abstract: Hexaconazole [(RS)-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl) hexan-2-ol] is a potent triazole fungicide and consists of a pair of enantiomers. Enantioselective degradation of hexaconazole was investigated in rat hepatic microsomes in vitro. Concentrations of (-)- and (+)-hexaconazole and enantiomer fraction were determined by high performance liquid chromatography with a cellulose-tris-(3,5-dimethylphenylcarbamate)-based chiral stationary phase. The t(1/2) of (-)-hexaconazole and (+)-hexaconazole were 23.70 and 13.95 min for rac- hexaconazole and 44.18 and 23.54 for enantiomers examined separately. Furthermore, hexaconazole is configurationally stable in rat hepatic microsomes, demonstrating no chiral inversion from the (-)-hexaconazole to (+)-hexaconazole or vice versa. Intrinsic metabolic clearance of (+)-hexaconazole is 1.12 times than that of (-)-hexaconazole. Interaction study revealed that there was competitive inhibition between (-)-hexaconazole and (+)-hexaconazole. In addition, there was a significant difference between the inhibitory concentration (IC(50)) of (-)- to (+)-hexaconazole and (+)- to (-)-hexaconazole [IC(50)(-)/(+)/IC(50)(+)/(-) = 1.88]. These results may have potential implications for better environmental and ecological risk assessment for hexaconazole.
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Ziheng
authors.initials: Z
authors.lastname: Dang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Shen
authors.forename: Wentao
authors.initials: W
authors.lastname: Zhu
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Xu
authors.forename: Donghui
authors.initials: D
authors.lastname: Liu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002138:Calibration; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D005659:Fungicides, Industrial / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013237:Stereoisomerism; D013379:Substrate Specificity; D014230:Triazoles / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D005659:Fungicides, Industrial; D014230:Triazoles; C409722:hexaconazole