青蒿素在不同溶剂中平衡溶解度和表观油水分配系数的测定

目的测定青蒿素在不同pH缓冲液和7种非极性溶剂中的平衡溶解度以及在正辛醇-水中的表观油水分配系数,为青蒿素新剂型的研究与开发提供实验基础。方法采用高效液相-柱后衍生化-紫外检测法测定青蒿素在不同pH缓冲溶液及7种非极性溶剂中的平衡溶解度;采用摇瓶法测定青蒿素的表观油水分配系数。结果 37℃时青蒿素在纯水中的平衡溶解度为82.4μg/mL,随着pH的增大平衡溶解度呈先增大（pH5.0～6.8）后减小（pH6.8～8.0）的趋势;37℃时青蒿素在肉豆蔻酸异丙酯（IPM）、油酸乙酯（EO）和中链甘油酸三酯（MCT）中平衡溶解度较大,分别为10.34、9.28、8.46mg/mL,青蒿素的正辛醇-水表观油水分配系数P为12.2（lgP=1.09）。结论青蒿素水溶性差,在非极性溶剂IPM、EO、MCT中平衡溶解度较大。

Determination of equilibrium solubility and apparent octanol/water partition coefficient of artemisinin in different solvents

Objective To determine the equilibrium solubility of artemisinin in buffer with different pH values and seven kinds of nonpolar solvents as well as its apparent octanol/water partition coefficient in octanol-water/buffer solution,thus to provide the experimental basis for the research and development of new preparation of artemisinin.Methods The equilibrium solubility of artemisinin in buffer with different pH values and seven kinds of nonpolar solvents was measured by HPLC with post-column derivatization and UV detection.Shaking flask method was adopted to determine the apparent octanol/water partition coefficient of artemisinin.Results The equilibrium solubility of artemisinin in water was 82.4 μg/mL at 37 ℃,and as the pH value increased,it increased first（pH values from 5.0 to 6.8） and decreased afterwards（pH values from 6.8 to 8.0）.At 37 ℃,the equilibrium solubility values of artemisinin in isopropyl myristate（IPM）,ethyl oleate（EO）,and medium-chain triglycerides（MCT） were 10.34,9.28,and 8.46 mg/mL,respectively.The apparent octanol-water partition coefficient of artemisinin was 12.2（lg P = 1.09）.Conclusion Artemisinin has poor water solubility,while its equilibrium solubility is higher in IPM,EO,and MCT.