目的 研究马钱子碱（BRU）与士的宁（STR）单体、马钱子总生物碱和马钱子提取物中活性成分BRU与STR在大鼠肝微粒体中的酶促反应动力学，考察BRU与STR单体、马钱子总生物碱和提取物中的BRU与STR在大鼠肝微粒体中的代谢差异。方法 采用LC-MS/MS法测定BRU和STR单体、总生物碱和提取物种BRU和STR在体外代谢系统中的含量变化，并计算其酶促反应动力学参数。结果 与BRU与STR单体组相比，马钱子总生物碱和提取物中2种单体成分的最大反应速度（V_max）和米氏常数（K_m）值均显著降低；与马钱子总碱组相比，马钱子提取物中2种单体成分的V_max和K_m值均显著升高。马钱子总生物碱组、单体成分组和马钱子提取物组中BRU的清除率（CL_int）之间无明显差异；而三者中STR的CL_int依次减少。结论 马钱子总碱、马钱子提取物中的BRU和STR及BRU与STR单体均可被肝微粒体代谢，且各组中BRU和STR的代谢动力学参数具有明显差异。

Objective To study the enzyme kinetics of brucine (BRU) and strychnine (STR), total alkaloids, and monomers active components of BRU and STR in extracts of Strychnos nux-vomica in rat liver microsomes, and investigate metabolic differences between BRU and STR monomer, total alkaloids, and BRU and STR in extracts in rat liver microsomes. Methods The contents of BRU and STR in the monomers, total alkaloids, and extracts in the metabolic system in vitro were measured by LC-MS/MS method, and the kinetic parameters of the enzyme were calculated. Results Compared with monomer group, K_m and V_max value of BRU and STR in total alkaloids and extracts of S. nux-vomica were obviously decreased; Compared with total alkaloids, K_m and V_max value of BRU and STR monomers in S. nux-vomica were obviously increased. The CL_int of BRU among total alkaloids and monomer extracts groups had no significantly difference; And the CL_int of STR in three groups was successively decreased. Conclusion Total alkaloids, BRU and STR in S. nux-vomica extracts, and BRU and STR monomer can be metabolized by the liver microsomes, and the pharmacokinetical parameters of BRU and STR in all groups have significant differences in metabolism.

国家自然科学基金资助项目（81660757）；江西省主要学科学术和技术带头人培养计划（20162BCB22015）