Stereoselective metabolism of benalaxyl in liver microsomes from rat and rabbit.
Benalaxyl (BX), methyl-N-phenylacetyl-N-2,6-xylyl alaninate, is a potent acylanilide fungicide and consist of a pair of enantiomers. The stereoselective metabolism of BX was investigated in rat and rabbit microsomes in vitro. The degradation kinetics and the enantiomer fraction (EF) were determined using normal high-performance liquid chromatography with diode array detection and a cellulose-tris-(3,5-dimethylphenylcarbamate)-based chiral stationary phase (CDMPC-CSP). The t(1/2) of (-)-R-BX and (+)-S-BX in rat liver microsomes were 22.35 and 10.66 min of rac-BX and 5.42 and 4.03 of BX enantiomers. However, the t(1/2) of (-)-R-BX and (+)-S-BX in rabbit liver microsomes were 11.75 and 15.26 min of rac-BX and 5.66 and 9.63 of BX enantiomers. The consequence was consistent with the stereoselective toxicokinetics of BX in vitro. There was no chiral inversion from the (-)-R-BX to (+)-S-BX or inversion from (+)-S-BX to (-)-R-BX in both rabbit and rat microsomes. These results suggested metabolism of BX enantiomers was stereoselective in rat and rabbit liver microsomes.
Zhang
Ping
P
Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
Zhu
Wentao
W
Dang
Ziheng
Z
Shen
Zhigang
Z
Xu
Xinyuan
X
Huang
Ledan
L
Zhou
Zhiqiang
Z
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005659:Fungicides, Industrial / Q000737:chemistry; D007700:Kinetics; D008862:Microsomes, Liver / Q000378:metabolism*; D048448:Phenylcarbamates / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D005659:Fungicides, Industrial; D048448:Phenylcarbamates; C065943:cellulose tris-3,5-dimethylphenyl-carbamate; C052866:benalaxyl; D002482:Cellulose; D000409:Alanine