Quantitative Retention‐Activity Relationship Studies by Liposome Electrokinetic Chromatography to Predict Skin Permeability

Abstract

AbstractLiposome electrokinetic chromatography (LEKC) provides a simple and facile approach for drug membrane interactions using liposome as a pseudostationary phase. This study evaluated the potential of LEKC for high‐throughput skin permeability profiled as an in vitro technique. A quantitative retention‐activity relationship (QRAR) model for the estimation of skin permeability was proposed. For the 16 structurally diverse chemicals, lg k correlated well with permeability values (R2=0.886). The predictive ability of the model was evaluated by cross‐validation. The result was compared to traditional quantitative structure‐activity relationship, QSAR, models using some molecular descriptors and physicochemical parameters. Interestingly, a single LEKC retention parameter was capable of describing the skin permeability, while three variables in QSAR were needed to achieve a similar correlation (R2=0.704). The QRAR models developed in this paper may be a useful method to screening new chemicals and in the early stage of development and selection of chemicals.