Departament de Química Analítica and Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Martí i Franquès, 1-11, E-08028 Barcelona, Spain.
Eur J Pharm Sci. 2013 Dec 18;50(5):557-68. doi: 10.1016/j.ejps.2013.04.005. Epub 2013 Apr 19.
Several chromatographic systems (three systems of high-performance liquid chromatography and two micellar electrokinetic chromatography systems) besides the reference octanol-water partition system are evaluated by a systematic procedure previously proposed in order to know their ability to model human skin permeation. The precision achieved when skin-water permeability coefficients are correlated against chromatographic retention factors is predicted within the framework of the solvation parameter model. It consists in estimating the contribution of error due to the biological and chromatographic data, as well as the error coming from the dissimilarity between the human skin permeation and the chromatographic systems. Both predictions and experimental tests show that all correlations are greatly affected by the considerable uncertainty of the skin permeability data and the error associated to the dissimilarity between the systems. Correlations with much better predictive abilities are achieved when the volume of the solute is used as additional variable, which illustrates the main roles of both lipophilicity and size of the solute to penetrate through the skin. In this way, the considered systems are able to give precise estimations of human skin permeability coefficients. In particular, the HPLC systems with common C18 columns provide the best performances in emulating the permeation of neutral compounds from aqueous solution through the human skin. As a result, a methodology based on easy, fast, and economical HPLC measurements in a common C18 column has been developed. After a validation based on training and test sets, the method has been applied with good results to the estimation of skin permeation of several hormones and pesticides.
几种色谱系统（三种高效液相色谱系统和两种胶束电动色谱系统）除了参考的辛醇-水分配系统外，还通过以前提出的系统程序进行了评估，以便了解它们模拟人体皮肤渗透的能力。在溶剂化参数模型的框架内，预测了将皮肤-水渗透率与色谱保留因子相关联时所达到的精度。这包括估计由于生物和色谱数据的误差以及由于人类皮肤渗透和色谱系统之间的不相似性而产生的误差的贡献。预测和实验测试均表明，所有相关性都受到皮肤渗透性数据的相当大的不确定性以及系统之间的不相似性相关联的误差的严重影响。当使用溶质的体积作为附加变量进行相关性时，可以获得更好的预测能力，这说明了溶质的亲脂性和大小对穿透皮肤的主要作用。通过这种方式，所考虑的系统能够对人体皮肤渗透率系数进行精确估计。特别是，带有普通 C18 柱的 HPLC 系统在模拟从水溶液中通过人体皮肤渗透中性化合物方面表现出最佳性能。因此，已经开发了一种基于在普通 C18 柱上进行简单，快速和经济的 HPLC 测量的方法。基于培训和测试集进行验证后，该方法已成功应用于估算几种激素和农药的皮肤渗透。
