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. Chirality, 2012. © 2012 Wiley Periodicals, Inc.