Stereochemistry of chiral pesticide uniconazole and enantioselective metabolism in rat liver microsomes

In this work, stereochemistry of uniconazole enantiomers and their metabolism behaviors in rat liver microsomes have been researched. Significance analysis has been applied in data processing. Absolute configurations of uniconazole enantiomers were identified through vibrational circular dichroism spectroscopy. According to their elution order from the chiral column using the CO 2 -methanol (80:20, v /v) mixture, two eluted fractions were determined to be ( R )-uniconazole and ( S )-uniconazole, respectively. A high-efficient and sensitive LC-MS/MS chiral analysis method was established for investigating the metabolism of uniconazole enantiomers in rat liver microsomes. The metabolic half-life of ( R )-uniconazole (38.7 min) in rat liver microsomes was half that of ( S )-enantiomer (74.5 min), and maximum velocity of metabolism, Michaelis constant of metabolism as well as the intrinsic metabolic clearance of ( R )-uniconazole were significantly higher than ( S )-enantiomer ( p < 0.05), which indicated that ( R )-uniconazole was preferentially metabolized in rat liver microsomes. By the virtue of molecular docking, ( R )-uniconazole exhibited a higher binding affinity to cytochrome CYP2D2 than ( S )-enantiomer, which corroborated well with the metabolism results. This work will shed light on the risk assessment of uniconazole toward human health and the ecological environment. • Enantioselective metabolism of uniconazole in rat liver microsomes was observed. • ( R )-uniconazole was preferentially metabolized in rat liver microsomes. • Molecular docking was used in illustrating enantioselective metabolism mechanism. • Docking results supported enantioselective binding of uniconazole with CYP2D2.