HPLC法测定柠檬苦素的平衡溶解度和表观油水分配系数

目的: 测定柠檬苦素的平衡溶解度及表观油水分配系数。 方法: HPLC法测定柠檬苦素的浓度,采用Dikma C₁₈色谱柱(5 μm,4.6 mm×250 mm),以乙腈-水(45:55)为流动相,流速为1.0 mL·min^-1,检测波长为210 nm,测定柠檬苦素在有机溶剂、水、缓冲液和表面活性剂溶液中的平衡溶解度,及其在正辛醇-水/缓冲液中的表观油水分配系数。 结果: 37℃时柠檬苦素在水中的平衡溶解度为6.85 μg·mL^-1,表观油水分配系数为65.55(lg P=1.82);在pH 4.0缓冲液中的平衡溶解度最小,表观油水分配系数最大;在二氯甲烷、乙腈、丙酮等有机溶剂中溶解度较大;吐温80对柠檬苦素有较强的增溶能力。 结论: 柠檬苦素水溶性差,易溶于有机溶剂,提高其溶解度可能会提高药物口服吸收效率及其口服制剂的生物利用度。

Objective: To determine the equilibrium solubility of limonin and its partition coefficients for the n-octanol-water / buffer solution system. Methods: A high performance liquid chromatography method was established to detect the concentration of limonin.The Dikma ODS(5 μm,4.6 mm×250 mm)column was adopted,the mobile phase was acetonitrile-water(45: 55)at the flow rate of 1.0 mL·min^-1,and the detection wavelength was 210 nm.The concentration of limonin in organic solvents,water,buffer solutions and surfactant solutions,and the partition coefficients for the n-octanol-water/buffer solution systems were detected. Results: The equilibrium solubility of limonin was 6.85 μg·mL^-1 in water at 37℃,its partition coefficient was 65.55(lg P=1.82)in the n-octanol-water system.The equilibrium solubility of limonin in pH 4.0 buffer phosphate was the minimum,but its partition coefficient in n-octanol/pH 4.0 buffer solution systems was the maximum.The equilibrium solubility of limonin was higher in organic solvents such as dichloromethane,acetonitrile,and acetone.Tween 80 was a good solubilizer for limonin. Conclusion: Limonin is not soluble in aqueous media and is easily soluble in organic solvents.The drug oral absorption efficiency and the bioavai lability of oral preparations can be improved by increasing the dissolution rate of linonin.