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目的:测定蝙蝠葛碱在不同pH条件下的平衡溶解度以及在正辛醇-缓冲液体系中的油水分配系数。方法:采用HPLC法测定蝙蝠葛碱的浓度,以饱和法测定平衡溶解度,采用摇瓶法-HPLC法测定蝙蝠葛碱在正辛醇和水相中浓度,从而计算油水分配系数。结果:37℃下蝙蝠葛碱的平衡溶解度随pH的升高而增大;油水分配系数随pH的升高而增大,在pH 6.8～8.0范围内(小肠的pH环境),蝙蝠葛碱的lgP约为0.5,说明其脂溶性较强。结论:蝙蝠葛碱平衡溶解度和油水分配系数都受pH的影响;本试验所建立的方法可准确测定蝙蝠葛碱的平衡溶解度和油水分配系数,并预测其体内过程。
OBJECTIVE: To determine the equilibrium solubility of dauricine at different pH and the oil-water partition coefficient in n-octanol-buffer system. Methods: The concentration of dauricine was determined by HPLC, the equilibrium solubility was determined by saturation method, and the concentration of dauricine in n-octanol and water phase was determined by shake flask method-HPLC method to calculate the oil-water partition coefficient. Results: The equilibrium solubility of dauricine increased with the increase of pH at 37 ℃. The partition coefficients of oil and water increased with the increase of pH. Under the conditions of pH 6.8-8.0 (pH environment of small intestine), dauricine lgP is about 0.5, indicating its fat-soluble stronger. Conclusion: The equilibrium solubility and oil-water partition coefficient of dauricine are affected by pH. The established method can accurately determine the equilibrium solubility and oil-water partition coefficient of dauricine and predict its in vivo process.