Comparative study on the interaction between 3 CYP2C9 allelic isoforms and benzbromarone by using LC-MS/MS method

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Lingli HeChangxiao Liu

Abstract

Benzbromarone is a uricosuric drug metabolized predominantly by cytochrome P450 2C9 from in vitro findings. Human CYP2C9 exhibits extensive genetic polymorphism and numbers of clinic studies have demonstrated that CYP2C9 genetic polymorphism has a significant influence on the pharmacokinetics of benzbromarone. But in vitro study on the interaction between CYP2C9 allelic isoforms and benzbromarone was rare. Here, an LC-MS/MS method was established and validated to determine the concentration of benzbromarone in different CYP2C9 enzyme incubation systems for the drug-enzyme interaction study. By selecting appropriate internal standard and optimizing separation system, including mobile phase, sample solvent and gradient elution condition, this LC-MS/MS method was developed with fine linearity (r2≥0.996), good reproducibility (RSD≤6.6%), high stability (92.37-114.67%), efficient recovery (91.23-109.82%) and acceptable matrix effect (110.54-115.31%). Based on this method, the interaction between 3 CYP2C9 allelic isoforms and benzbromarone was researched by kinetics parameters (Km, Vmax, Clint). As a result, CYP2C9*1 displayed the highest metabolic activity towards benzbromarone, CYP2C9*2 showed a little lower catalytic activity than...Continue Reading

Citations

Apr 3, 2020·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Hui HeChao Yu
Aug 20, 2020·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Mizuki YamaneToshito Nakagawa

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