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.