高效液相色谱法测定特考韦瑞的平衡溶解度和油水分配系数

Determination of the equilibrium solubility of tecovirimat and its apparent oil/water partition coefficients using HPLC

目的用高效液相色谱法(HPLC)测定特考韦瑞(ST-246)在37℃水和不同pH缓冲液的平衡溶解度,以及在正辛醇-水/缓冲液系统的油水分配系数。方法采用摇瓶法测定平衡溶解度,通过药物分配平衡后在油相及水相的浓度比,计算油水分配系数。结果 ST-246在37℃水的平衡溶解度为3.35 mg/L,ST-246的表观油水分配系数为230.49(lgP=2.36),在正辛醇/pH4.0缓冲液的油水分配系数最大,为779(lgP=2.89)。结论 ST-246的水溶性较差,脂溶性不佳,其水中溶解度呈pH依赖性,增大pH可增加其溶解度。

Objective To determine the equilibrium solubility and oil/water apparent partition coefficients（lgP） of tecovirimat（ST-246） in a series of test solutions of different pH using HPLC.Methods The equilibrium solubility was determined by saturation methods,and P was calculated with the concentration ratio of the drug in oil and water phase after partition equilibrium.Results The equilibrium solubility of ST-246 is 3.35 mg/L in water at 37℃,and the oil/water lgP of ST-246 was 2.36.It has the highest partition coefficients in n-octanol/pH4.0 buffer solution system.Conclusion ST-246 has poor watersolubility and liposolubility.ST-246 is not easily soluble and a higher pH can improve its equilibrium solubility.