Stereoselective Degradation of alpha‐Cypermethrin and Its Enantiomers in Rat Liver Microsomes

Alpha‐cypermethrin (α‐CP), [(RS)‐a‐cyano‐3‐phenoxy benzyl (1RS)‐cis‐3‐(2, 2‐dichlorovinyl)‐2, 2‐dimethylcyclopropanecarboxylate], comprises a diastereoisomer pair of cypermethrin, which are (+)‐(1R‐cis‐αS)–CP (insecticidal) and (−)‐(1S‐cis‐αR)–CP (inactive). In this experiment, the stereoselective degradation of α‐CP was investigated in rat liver microsomes by high‐performance liquid chromatography (HPLC) with a cellulose‐tris‐ (3, 5‐dimethylphenylcarbamate)‐based chiral stationary phase. The results revealed that the degradation of (−)‐(1S‐cis‐αR)‐CP was much faster than (+)‐(1R‐cis‐αS)‐CP both in enantiomer monomers and rac ‐α‐CP. As for the enzyme kinetic parameters, there were some variances between rac ‐α‐CP and the enantiomer monomers. In rac ‐α‐CP, the V max and CL int of (+)‐(1R‐cis‐αS)–CP (5105.22 ± 326.26 nM/min/mg protein and 189.64 mL/min/mg protein) were about one‐half of those of (−)‐(1S‐cis‐αR)–CP (9308.57 ± 772.24 nM/min/mg protein and 352.19 mL/min/mg protein), while the K m of the two α‐CP enantiomers were similar. However, in the enantiomer monomers of α‐CP, the V max and K m of (+)‐(1R‐cis‐αS) ‐CP were 2‐fold and 5‐fold of (−)‐(1S‐cis‐αR)‐CP, respectively, which showed a significant difference with rac ‐α‐CP. The CL int of (+)‐(1R‐cis‐αS)–CP (140.97 mL/min/mg protein) was still about one‐half of (−)‐(1S‐cis‐αR)–CP (325.72 mL/min/mg protein) in enantiomer monomers. The interaction of enantiomers of α‐CP in rat liver microsomes was researched and the results showed that there were different interactions between the IC 50 of (−)‐ to (+)‐(1R‐cis‐αS)‐CP and (+)‐ to (−)‐(1S‐cis‐αR)‐CP(IC 50(−)/(+) / IC 50(+)/(−)  = 0.61). Chirality 28:58–64, 2016 . © 2015 Wiley Periodicals, Inc.