摘要
目的:采用2种不同方法测定不同pH值下的罗格列酮油水分配系数(logP)。方法:以正辛醇-水为模拟系统,采用摇瓶-紫外分光光度法,测定在不同pH值(0.95、2.0、3.0、4.0、5.07、5.7、6.55、7.06、7.5、8.15、9.21)下罗格列酮在水相和有机相中的药物浓度以计算logP值,并与采用计算机Pallas软件得到的logP预测值比较。结果:当pH<4时,罗格列酮的logP<1;当pH为5～9时,罗格列酮的logP>1。实际测定值与Pallas软件预测的logP值随pH变化趋势相一致。结论:罗格列酮在pH<3时以酸式盐的形式存在,水溶性较好;而在pH5～9时以游离碱形式存在,脂溶性较好。Pallas软件可用于预测药物的logP值。
OBJECTIVE： To determine the oil-water partition coefficients （logP） ofrosiglitazone at different pH values by two kinds of methods. METHODS： A shake flask-ultraviolet spectrophotometry method was used to determine plasma concentration of rosiglitazone in water phase and organic phase at variable pH values （0.95, 2.0, 3.0, 4.0, 5.07, 5.7, 6.55, 7.06, 7.5, 8.15, 9.21） to calculate logP by using with n-caprylic alcohol-water as simulation system. Above logP values were compared with that calculated by Pallas software. RESULTS： The logP value was lower than 1 when pH value was lower than 4; the logP value was higher than 1 when pH value was ranged from 5 to 9. Measured logP values were in good agreement with that calculated by Pallas software. CONCLUSION： Rosiglitazone exists in the form of hydrochloride salt with good water solubility （pH〈3） while it exists in the form of molecule with sound liposolubility （pH 5-9）. Pallas software is suitable for predicting the logP value.
出处
《中国药房》
CAS
CSCD
北大核心
2010年第5期409-411,共3页
China Pharmacy
基金
重庆市自然科学基金资助项目(CSTC2006BB5286)
