洋川芎內酯I與血漿蛋白結合率的測定

李恩華 沈佳偉

【摘 要】 目的：研究洋川芎內酯I與大鼠和人血漿蛋白結合情況。方法：采用平衡透析法測定洋川芎內酯I與大鼠和人血漿蛋白結合率，以液相質譜聯用法測定透析內外液中洋川芎內酯I的濃度，計算其血漿蛋白結合率。結果：血漿中其他成分對測定無干擾，洋川芎內酯I在0.05～10μM濃度范圍內線性關系均良好，精密度及穩定性結果均符合方法學要求；實驗選擇紫杉醇為陽性對照，孵育8h后，紫杉醇與大鼠和人血漿蛋白結合分別為92.3%～94.5% 和93.8%～97.2%，與文獻報道的范圍88%～98%一致。孵育8h后，洋川芎內酯I與大鼠血漿蛋白結合率為83.5%～86.5%；與人血漿蛋白結合率為82.1%～83.9%。結論：該方法操作簡便、快速，靈敏度高，能滿足生物樣品的分析要求。洋川芎內酯I與大鼠和人血漿蛋白結合較強 （> 80%）。

【關鍵詞】 洋川芎內酯I；血漿蛋白結合率；平衡透析法；液相質譜聯用

【中圖分類號】R284 【文獻標志碼】 A 【文章編號】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

洋川芎內酯I是傘形科植物川芎Ligusticum Chuanxiong Hort.的主要活性成分之一[1]。藥理研究表明，洋川芎內酯I能夠透過血腦屏障對腦部疾病尤其是偏頭痛發揮一定的治療作用[2-3]。藥動學表明，洋川芎內酯I經口服給藥后，能被快速吸收進入血液循環，并不同程度地分布到各組織中[4]。

藥物在體內轉運、轉化過程中，可與組織蛋白（包括受體）和體液蛋白相結合，因此在組織和體液中除含有游離的藥物外，還含有結合的藥物。藥物與血漿蛋白的結合與藥物的體內過程密切相關。如藥物與血漿蛋白呈濃度依賴性結合時引起非線性藥代動力學。與……