Stereoselective degradation of metalaxyl and its enantiomers in rat and rabbit hepatic microsomes in vitro

Abstract

1. The stereoselective degradations of racemate metalaxyl (rac-MX) and its single enantiomers in rat and rabbit hepatic microsomes were assayed by a chiral high-performance liquid chromatography method.

2. The t_1/2 of (+)-S-MX in rat liver microsomes was between 7–8 min tested by rac-MX and the individual (+)-S-enantiomer, respectively, and that for (−)-R-MX was 15–16 min. In contrast, t_1/2 in rabbit liver microsomes was much longer and showed great difference when using racemate and single enantiomer, which was similar to the results of in vivo study.

3. The enantioselectivity in rat hepatic microsomes was more evident and the degradations of MX enantiomers in rat and rabbit hepatic microsomes were Nicotinamide adenine dinucleotide phosphate-dependent.

4. Michaelis constant (K_m) and intrinsic metabolic clearance (CL_int) of (+)-S-MX were larger than that of (−)-R-MX and there was no chiral inversion from (+)-S-MX to (−)-R-MX or vice versa in both rat and rabbit hepatic microsomes.

Keywords:

• Metalaxyl
• stereoselective degradation
• hepatic microsomes
• rat
• rabbit

Acknowledgments

We gratefully acknowledge financial support from National Natural Science Foundation of China Contract grant number: 20877100, 20707038). Specialized Research Fund for the Doctoral program of Higher Education (Project No. 20090008120016). Foundation for the Author of National Excellent Doctoral Dissertation, Program for New Century Excellent Talents in University, the New-Star of Science and Technology supported by Beijing Metropolis.

Declaration of interest

The authors report no conflicts of interest.