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 (K_m, V_max, Cl_int). As a result, CYP2C9*1 displayed the highest metabolic activity towards benzbromarone, CYP2C9*2 showed a little lower catalytic activity than CYP2C9*1 (relative clearance/*1 = 85.86%), CYP2C9*3 showed the lowest catalytic activity (relative clearance/*1 = 21.57%). The result illustrated that various CYP2C9 allelic isoforms showed different enzymatic activities towards benzbromarone, which could offer effective consultation for personalized administration in clinic.

苯溴马隆是一种尿酸尿酸药物，主要通过体外发现的细胞色素P450 2C9代谢。人类CYP2C9具有广泛的遗传多态性，许多临床研究表明，CYP2C9遗传多态性对苯溴马隆的药代动力学有重要影响。但是在体外CYP2C9等位基因亚型与苯溴马隆之间相互作用的研究很少。在这里，建立了LC-MS / MS方法并进行了验证，以确定在不同的CYP2C9酶孵育系统中用于药物-酶相互作用研究的苯溴马隆的浓度。通过选择合适的内标和优化分离系统，包括流动相，样品溶剂和梯度洗脱条件，该LC-MS / MS法用细线性关系（r开发²  ≥0.996），良好的再现性（RSD≤6.6％），高稳定性（92.37–114.67％），有效回收率（91.23–109.82％）和可接受的基质效应（110.54–115.31％）。基于该方法，通过动力学参数（K _m，V _max）研究了3种CYP2C9等位基因同工型与苯溴马隆之间的相互作用。，Cl _int）。结果，CYP2C9 * 1表现出最高的对苯溴马隆的代谢活性，CYP2C9 * 2表现出比CYP2C9 * 1略低的催化活性（相对清除率/ * 1 = 85.86％），CYP2C9 * 3表现出最低的催化活性（相对清除率） / * 1 = 21.57％）。结果表明，多种CYP2C9等位基因亚型对苯溴马隆表现出不同的酶促活性，可为临床个性化给药提供有效的咨询。