HPLC法测定盐酸吲哚美辛2-[2-(6-甲氧基-2-萘基)吗啉基]乙酯的平衡溶解度和脂水分配系数  

Determination of equilibrium solubility and apparent oil/water partition coefficient of indomethacin prodrug by HPLC

作　　者：凌伟[1,2] 石磊[3] 戴智勇[1] 徐智[1] 

机构地区：[1]中南大学湘雅医院,长沙410008 [2]中南大学药学院,长沙410013 [3]湖南大学化学化工学院,长沙410082

出　　处：《中国新药杂志》2011年第9期833-836,共4页Chinese Journal of New Drugs

基　　金：2009年湖南省长沙市重点项目(K0901077-31)

摘　　要：目的:测定盐酸吲哚美辛2-[2-(6-甲氧基-2-萘基)吗啉基]乙酯在乙醇、乙腈、丙酮、乙酸乙酯等溶剂中的平衡溶解度以及在正辛醇-水和正辛醇-缓冲液体系中的表观油水分配系数。方法:采用HPLC法测定盐酸吲哚美辛2-[2-(6-甲氧基-2-萘基)吗啉基]乙酯的浓度,采用摇瓶法测定其表观油水分配系数。结果:25℃时盐酸吲哚美辛2-[2-(6-甲氧基-2-萘基)吗啉基]乙酯在乙醇、乙腈、丙酮、乙酸乙酯中的平衡溶解度分别为31.36,141.50,575.77,598.68 g.L-1。pH=4时此目的化合物的平衡溶解度最小,而表观油水分配系数最大。结论:盐酸吲哚美辛2-[2-(6-甲氧基-2-萘基)吗啉基]乙酯的平衡溶解度及油水分配系数与介质的pH有关。其水溶性较差,脂溶性好。Objective：To determine the equilibrium solubility of 2-[2-（6-methoxynaphthalen-2-yl）morpholino]ethyl ester of indomethacin in various solvents such as ethanol acetonitrile acetone and ethyl acetate and its apparent oil/water partition coefficients in the n-octanol-water/buffer solution systems.Methods：The concentration of indomethacin prodrug was determined by HPLC,and the apparent oil/water partition coefficient was determined by shaking flask method.Results：The higher equilibrium solubility of indomethacin prodrug at 25 ℃ was 31.36,141.50,575.77 or 598.68 g·L-1 in ethanol,acetonitrile,acetone or ethyl acetate,respectively.The equilibrium solubility of indomethacin prodrug was the lowest;however it had the highest partition coefficients in n-octanol/pH 4 buffer solution system.Conclusion：The equilibrium solubility and apparent oil/water partition coefficients of indomethacin prodrug are correlated to pH of the medium.The prodrug is more soluble in oil than in water.

关 键 词：盐酸吲哚美辛2-[2-(6-甲氧基-2-萘基)吗啉基]乙酯 平衡溶解度 表观油水分配系数 高效液相色谱法 

分 类 号：R971.1[医药卫生—药品]