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本文以13个对氨基苯甲酸酯化合物为模型药物,研究它们的HPLC保留行为与透皮速率的关系。测定了该系列化合物的正辛醇/水分配系数,在20％聚乙二醇400生理盐水中的溶解度及其饱和溶液通过去毛大鼠腹部离体皮肤的稳态流率,并计算相应的渗透系数。以不同的甲醇:水配比的流动相,测定各化合物的保留时间,求取容量因子和保留指数。结果表明,化合物的容量因子的对数值和保留指数不但与它们的正辛醇/水分配系数的对数有很好的线性相关,而且它们都可代入Hansch方程来预测这些化合物的稳态流率与渗透系数。由于HPLC容量因子与保留指数的测定方法简便、准确,因而可代替费时繁杂与不稳定的分配系数测定,进行药物透皮研究的构效关系分析。
In this paper, 13 p-aminobenzoate compounds were used as model drugs to study the relationship between their HPLC retention behavior and transdermal rate. The n-octanol / water partition coefficient, the solubility in saturated solution of 20% polyethylene glycol 400 and the steady-state flow rate of the saturated solution in the isolated skin of abdomen of the dehairing rats were determined. Permeability coefficient. Different methanol: water ratio of the mobile phase, the determination of retention time of each compound, to obtain the capacity factor and retention index. The results showed that the logarithm and retention indices of the capacity factors of the compounds were not only linearly correlated with the logarithm of their n-octanol / water partition coefficients, but they all could be substituted into the Hansch equation to predict the steady-state flow rates of these compounds And permeability coefficient. Due to the simple and accurate HPLC capacity factor and retention index determination method, the structure-activity relationship analysis of drug transdermal study can be performed instead of time-consuming and unstable determination of partition coefficient.