IAM Chromatographic Models of Skin Permeation

Chromatographic retention factor log k(IAM) obtained from IAM HPLC chromatography with buffered aqueous mobile phases and calculated molecular descriptors (surface area—S(a); molar volume—V(M); polar surface area—PSA; count of freely rotable bonds—FRB; H-bond acceptor count—HA; energy of the highest occupied molecular orbital—E(HOMO); energy of the lowest unoccupied orbital—E(LUMO); and polarizability—α) obtained for a group of 160 structurally unrelated compounds were tested in order to generate useful models of solutes’ skin permeability coefficient log K(p). It was established that log k(IAM) 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 k(IAM) 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 K(p) values.