Enantioselective degradation of hexaconazole in rat hepatic microsomes in vitro

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.