HPLC法测定恩替卡韦的平衡溶解度和表观油水分配系数

Determination of equilibrium solubility of entecavir and its apparent oil/water partition coefficient by HPLC

目的考察恩替卡韦在不同介质中的平衡溶解度及其在正辛醇-水和正辛醇-缓冲液体系中的表观油水分配系数,为后续的制剂研究奠定基础。方法采用摇瓶-高效液相色谱法测定恩替卡韦在水中和不同p H值缓冲液中的平衡溶解度及表观油水分配系数。结果 37 oC时恩替卡韦在水中的平衡溶解度为2.53 g·L–1,碱性条件下的溶解度较低,酸性条件下的溶解度增大;恩替卡韦在不同p H值的正辛醇-缓冲液体系中的表观油水分配系数均较小。结论本文建立的测定方法简单可行,37 oC时恩替卡韦微溶于水,且溶解度随p H值减小而增大,表观油水分配系数随p H值减小而减小。

Objective To detemine the equilibrium solubility of entecavir in various media and its apparent oil/water partition coefficient in the n-octanol-water/buffer solution systems, which will build up a basis for the further research of its preparations. Methods A shake flask-high performance liquid chromatography(HPLC) method was developed to determine the equilibrium solubility of entecavir in water and different p H buffer solutions and its apparent oil/water partition coefficient. Results The equilibrium solubility of entecavir was 2.53 mg·m L–1 in water at 37 oC. Furthermore, the values were lower in basic buffer solutions and increased in acid buffer solutions. In addition, the values of apparent oil/water partition coefficient of entecavir were low in n-octanol-water/buffer solution systems with different p H values. Conclusions A simple and feasible method was established in this study. It was found that entecavir is slightly soluble in water at 37 oC, and its solubility and apparent oil/water partition coefficient are separately increased and decreased as p H value reduces.