HPLC法测定洋川芎内酯Ⅰ的平衡溶解度和表观油水分配系数

目的:测定洋川芎内酯Ⅰ的平衡溶解度和油水分配系数,为设计洋川芎内酯Ⅰ新剂型提供基础。方法:采用HPLC法测定洋川芎内酯Ⅰ的浓度,使用Megres-C₁₈色谱柱(5 μm,4.6 mm×100 mm),以乙腈-水(1:3, v/v)为流动相,流速为1.0 mL·min^-1,检测波长278 nm,测定洋川芎内酯Ⅰ在水和不同pH缓冲液介质中的平衡溶解度,及其在正辛醇-水/缓冲液中的表观油水分配系数。结果:37℃下洋川芎内酯Ⅰ在水中的平衡溶解度为34.31 mg·mL^-1;洋川芎内酯Ⅰ在pH≥9.0的缓冲液溶剂体系中不稳定。在正辛醇-水体系中的表观油水分配系数13.43(lg P_app=1.13);pH值对洋川芎内酯Ⅰ表观油水分配系数影响不大。结论:洋川芎内酯Ⅰ水溶性好,表观油水分配系数适中,相对分子质量较小,可借此解析其快速入血入脑过程,预测洋川芎内酯Ⅰ有较好的应用价值。

Objective:To determine the equilibrium solubility of senkyunoide Ⅰ and its partition coefficients for the n-octanol-water/buffer solution systems,so as to provide a basis for new formulations designing. Methods:A high performance liquid chromatography method was established to detect the concentration of senkyunolide Ⅰ.The Megres ODS(5 μm,4.6 mm×100 mm)column was adopted,the mobile phase was acetonitrile-water(1:3, v/v)at a flow rate of 1.0 mL·min^-1,and the detection wavelength was 278 nm.The concentration of senkyunolide Ⅰ in different pH solutions and the partition coefficients for the n-octanol-water and n-octanol-buffer solution systems were detected. Results:The equilibrium solubility reached a maximum of 34.31 mg·mL^-1in water at 37℃.Senk yunolide Ⅰ was instable in solvent systems pH≥9.0.Partition coefficient of senkyunolideⅠwas 13.43(lg P_app=1.13) in the n-octanol-water system;there was no significant effect of pH to partition coefficient of senkyunolide Ⅰ. Conclusions:The study showed that senkyunolide Ⅰ is soluble,the partition coefficient of senkyunolide Ⅰ is moderate,and the relative molecular mass of senkyunolide Ⅰ is small.Therefore,we can explain why senkyunolide Ⅰ can quickly reach into blood and brain.Senkyunolide Ⅰ can be predicted with a good application value.

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