李恩华 沈佳伟

【摘 要】 目的：研究洋川芎内酯I与大鼠和人血浆蛋白结合情况。方法：采用平衡透析法測定洋川芎内酯I与大鼠和人血浆蛋白结合率，以液相质谱联用法测定透析内外液中洋川芎内酯I的浓度，计算其血浆蛋白结合率。结果：血浆中其他成分对测定无干扰，洋川芎内酯I在0.05～10μM浓度范围内线性关系均良好，精密度及稳定性结果均符合方法学要求；实验选择紫杉醇为阳性对照，孵育8h后，紫杉醇与大鼠和人血浆蛋白结合分别为92.3%～94.5% 和93.8%～97.2%，与文献报道的范围88%～98%一致。孵育8h后，洋川芎内酯I与大鼠血浆蛋白结合率为83.5%～86.5%；与人血浆蛋白结合率为82.1%～83.9%。结论：该方法操作简便、快速，灵敏度高，能满足生物样品的分析要求。洋川芎内酯I与大鼠和人血浆蛋白结合较强 （> 80%）。

【关键词】 洋川芎内酯I；血浆蛋白结合率；平衡透析法；液相质谱联用

【中图分类号】R284 【文献标志码】 A 【文章编号】1007-8517（2018）01-0044-04

Abstract：Objective To determine plasma protein binding ratio of senkyunolide I in rat and human plasma.Methods The plasma samples were precipitated by acetonitrile and analyzed by high performance liquid chromatography-mass spectrometry （LC-MS/MS）.The rapid equilibrium dialysis was carried out to determine the protein binding rate of senkyunolide I in rat and human plasma.Results The results showed that no substances from plasma interfered the determination of senkyunolide I.The calibration curve of the analytes was in good linearity in certain range of 0.05～10 μM.The precision and stability of the analytes met the methodology requirements.Taxol was used as the positive control， after incubation for 8 h， the binding ratio were 92.3%～94.5% and 93.8%～97.2% for rat and human， respectively， which was in accordance with the literature.The binding ratio of senkyunolide I were 83.5%～86.5% and 82.1%～83.9% for rat and human， respectively.Conclusion The method was proved to be simple， rapid and sensitive.And senkyunolide I displayed a high plasma protein binding ratio （> 80%）.

Keywords：Senkyunolide I；Plasma Protein Binding；Rapid Equilibrium Dialysis； LC/MS/MS

洋川芎内酯I是伞形科植物川芎Ligusticum Chuanxiong Hort.的主要活性成分之一[1]。药理研究表明，洋川芎内酯I能够透过血脑屏障对脑部疾病尤其是偏头痛发挥一定的治疗作用[2-3]。药动学表明，洋川芎内酯I经口服给药后，能被快速吸收进入血液循环，并不同程度地分布到各组织中[4]。

药物在体内转运、转化过程中，可与组织蛋白（包括受体）和体液蛋白相结合，因此在组织和体液中除含有游离的药物外，还含有结合的药物。药物与血浆蛋白的结合与药物的体内过程密切相关。如药物与血浆蛋白呈浓度依赖性结合时引起非线性药代动力学。与……