IAM Chromatographic Models of Skin Permeation.

Chromatographic retention factor log obtained from IAM HPLC chromatography with buffered aqueous mobile phases and calculated molecular descriptors (surface area-; molar volume-; polar surface area-; count of freely rotable bonds-; H-bond acceptor count-; energy of the highest occupied molecular orbital-; energy of the lowest unoccupied orbital-; and polarizability-) obtained for a group of 160 structurally unrelated compounds were tested in order to generate useful models of solutes' skin permeability coefficient log . It was established that log obtained in the conditions described in this study is not sufficient as a sole predictor of the skin permeability coefficient. Simple put, potentially useful models based on log and readily available calculated descriptors, accounting for 85 to 91% of the total variability, were generated using Multiple Linear Regression (MLR).The models proposed in the study were tested on a group of 20 compounds with known experimental log values.