药物透皮速率与高效液相色谱保留行为的相关性

The Relationship between Percutaneous Rate of Drug and Its HPLC Retention Beharior

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。

A series of 13 p - aminobenzoate esters were selected as model drugs to study correlations between HPLC retention parameters and percutaneous rate. The octanol/water partition coefficient and solubility of these compounds were determined and their permeation through rat skin was measured using a Franz diffusion cell. Capacity factor and retention index were used as HPLC retention parameters and calculated from their retention times . The results indicate that for the p - aminobenzoate esters studied, the capacity factors and retention indices obtained in our expermental conditions are indicators of relative lipophilicity of drugs and can be used to predict their steady - state fluxes and permeation coefficients by using the Hansch equation. They are easy to obtain and reproducible enough to substitute for the more laborious and innacurate partition coefficient values.