间尼索地平对映体在人肝微粒体中的酶促反应动力学研究

目的: 研究间尼索地平对映体在人肝微粒体中的酶促反应动力学,计算其酶促反应动力学参数,并对R型和S型间尼索地平的酶促反应动力学过程进行比较.方法: 以尼莫地平为内标,建立液相色谱-质谱联用(LC-MS)方法分别测定体外孵育人肝微粒体后R型、S型间尼索地平含量,采用Linewrave-Burk作图法处理数据,以底物消除法计算酶促动力学参数K_m和V_max.结果: R-间尼索地平K_m=71.67 μmol·L^-1,V_max=2.513 μmol·min^-1·mg^-1;S-间尼索地平K_m=72.86 μmol·L^-1,V_max=2.534 μmol·min^-1·mg^-1.结论: 该方法简单、可靠,适用于间尼索地平的体外代谢研究,R型和S型间尼索地平的酶促反应动力学过程无明显差异.

Objective: To study the enzyme kinetics of m-nisoldipine enantiomers in human liver microsomes, calculate the enzyme kinetic parameters and compare the enzyme kinetic processes of (R)-m-nisoldipine and(S)-m-nisoldipine. Methods: An LC-MS method was established for quantitative analysis of m-nisoldipine enantiomers with nimodipine as internal standard.Linewrave-Burk graphic method was used to calculate the enzyme kinetic parameters V_max and K_m. Results: The enzyme kinetic parameters were as follows:(R)-m-nisoldipine K_m=71.67 μmol·L^-1, V_max=2.513 μmol·min^-1·mg^-1;(S)-m-nisoldipine K_m=72.86 μmol·L^-1, V_max=2.534 μmol·min^-1·mg^-1. Conclusion: The method was simple and reliable for the in vitro metabolism research of m-nisoldipine.There was no significant difference between(R)-m-nisoldipine and(S)-m-nisoldipine in enzyme kinetics.