Stereoselective Degradation of Chiral Fungicide Myclobutanil in Rat Liver Microsomes†. Issue 1 (19th November 2013) - Yan, Jin
ABSTRACT Myclobutanil, (RS)‐2‐(4‐chlorophenyl)‐2‐(1H‐1, 2, 4‐triazol‐1‐ylmethyl)hexanenitrile is a broad‐spectrum systemic triazole fungicide which consists of a pair of enantiomers. The stereoselective degradation of myclobutanil was investigated in rat liver microsomes. The concentrations of myclobutanil enantiomers were determined by high‐performance liquid chromatography (HPLC) with a cellulose‐tris‐(3, 5‐dimethyl‐phenylcarbamate)‐based chiral stationary phase (CDMPC‐CSP) under reversed phase condition. The t1/2 of (+)‐myclobutanil is 8.49 min, while the t1/2 of (–)‐myclobutanil is 96.27 min. Such consequences clearly indicated that the degradation of myclobutanil in rat liver microsomes was stereoselective and the degradation rate of (+)‐myclobutanil was much faster than (–)‐myclobutanil. In addition, significant differences between two enantiomers were also observed in enzyme kinetic parameters. The Vmax of (+)‐myclobutanil was about 4‐fold of (–)‐myclobutanil and the CLint of (+)‐myclobutanil was three times as much as (–)‐myclobutanil after incubation in rat liver microsomes. Corresponding consequences may shed light on the environmental and ecological risk assessment for myclobutanil and may improve human health. Chirality 26:51–55, 2013. © 2013 Wiley Periodicals, Inc.