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Enantioselective degradation of hexaconazole in rat hepatic microsomes in vitro
Author(s) -
Zhang Ping,
Dang Ziheng,
Shen Zhigang,
Zhu Wentao,
Xu Xinyuan,
Liu Donghui,
Zhou Zhiqiang
Publication year - 2012
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.21993
Subject(s) - hexaconazole , chemistry , enantiomer , enantioselective synthesis , microsome , stereochemistry , in vitro , biochemistry , fungicide , botany , biology , catalysis , carbendazim
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. Chirality, 2012. © 2012 Wiley Periodicals, Inc.