秋水仙碱油水分配系数和平衡溶解度的测定

目的:测定秋水仙碱在正辛醇-水系统中的油水分配系数及其在不同p H水溶液中的平衡溶解度,为该成分的制剂开发提供参考。方法:采用摇瓶法和高效液相色谱法(HPLC)测定秋水仙碱在正辛醇-水中的油水分配系数及其在不同p H水溶液中的平衡溶解度,色谱条件为C_(18)色谱柱,流动相甲醇-水(40∶60),检测波长254 nm。结果:秋水仙碱在水及p H为1.2,2.0,4.0,6.8,7.4缓冲液中的平衡溶解度分别为12.99,14.77,15.32,23.99,12.28,12.36 g·L~(-1),油水分配系数分别为4.05,6.62,6.31,5.34,8.88,7.13。结论:秋水仙碱的油水分配系数和平衡溶解度均与p H无相关性,秋水仙碱属于高溶解性、低渗透性药物,可能存在除油水分配系数以外的因素限制秋水仙碱的渗透性。

Determination of Oil-water Partition Coefficient and Equilibrium Solubility of Colchicine

Objective: To determine oil-water partition coefficient and equilibrium solubility of colchicine in water system with different pH. Method: The content of colchicine was determined by HPLC,apparent octanol-water partition coefficient and equilibrium solubility of colchicine was measured by shake-flask method.Chromatographic conditions were C₁₈ column,methanol-water (40 : 60) as mobile phase and detection wavelength at 254 nm. Result: In solutions of water,pH 1.2,2.0,4.0,6.8 and 7.4 buffer,equilibrium solubilities of colchicine were 12.99,14.77,15.32,23.99,12.28, 12.36 g · L^-1,partition coefficients were 4.05,6.62,6.31,5.34,8.88 and 7.13,respectively. Conclusion: There is no correlation between colchicine oil-water partition coefficient,solubility and pH.Colchicine has characteristics of high solubility and low permeability.There may be some factors that restrict colchicine's permeability except oil-water partition coefficient.