中文摘要：

目的：研究去甲异波尔定在大鼠肝微粒体中的葡萄糖醛酸化酶促反应动力学。方法：优化去甲异波尔定与大鼠肝微粒体的反应体系,采用超高效液相色谱-质谱联用技术定量检测孵育体系中去甲波尔定代谢产物去甲异波尔定-9-O-α-葡萄糖醛酸苷的浓度,并应用Linewearve-Burk作图分析数据,计算酶促动力学常数。结果：去甲异波尔定-9-O-α-葡萄糖醛酸苷的酶促反应动力学参数Km40.7μmol.L-1,Vmax=909.1 pmol.（min.mg pro）-1,肝清除率CLint（Vmax/Km）=22.3μL.min-1.mg-1。结论：该方法简单、快速、可靠,适应于去甲异波尔定的葡萄糖醛酸化代谢研究;葡萄糖醛酸化是去甲异波尔定代谢的重要途径之一,提示葡萄糖醛酸转移酶的基因多态性及相关性的药物相互作用引起的去甲异波尔定活性和毒性作用的变化值得进一步关注。

英文摘要：

Objective： To investigate the enzyme kinetics of norisoboldine glucuronidation in rat liver microsomes. Method： An UPLC-MS method was developed for determination of norisoboldine-9-O-a-glucuronide, a major metabolite of norisoboldine, in liver microsomes incubation system with sinomenine as internal standard. An optimum incubation system was found and the enzyme kinetics parameters of norisoboldine-9-0-a-glucuronide were analyzed and calculated with Linewearve-Burk graphic method. Result： The Km, Vmax and CZint （ Vmax/gm ） of norisoboldine-9-0-a-glucuronide were 40.7 μmol·L^（-1） 909. 1 pmol@（min.mg pro） ^（-1） and 22.3 txL-min^（-1）·mg^（-1） respectively. Conclusion： This method is simple, specific and reliable, which is suitable for the in vitro research of norisoboldine glucuronidation.