<p>The solute-solvent interactions that determine distribution between water and a model liposome, representative of biological cell membranes, are studied by liposome electrokinetic chromatography (LEKC) and characterized and quantified by the Abraham Solvation Parameter Model. Because of the limited solubility of usual liposome markers, several methods to determine the liposome mobility, required to calculate solute mass distribution ratios, have been tested and a new one, based on the Abraham model applied to homologous series, is proposed with successful results. Characterization of the LEKC system by the Abraham model shows that the most significant interactions ruling liposome partition are the creation of solute cavities in the phases, which is easier in the liposome than in water, and hydrogen bonding from liposome and water phases to the&#xa0;solute (solute hydrogen bond basicity), which is stronger from the aqueous phase. To a minor degree, solute dipolarity and hydrogen bond acidity (hydrogen bonding from solutes to phases) contribute to partition too. Dipolarity interactions favor partition to water rather than to the liposome. However, and contrary to solute hydrogen bond basicity, solute hydrogen bond acidity favors partition to the&#xa0;liposome, revealing that the studied liposome is a better hydrogen bond acceptor than water. Polarizability interactions by solute <i>n</i> and <i>π</i> electrons are not significant. Comparison of the LEKC system Abraham characterization parameters to those of several in vivo and in vitro blood-organ partitions, characterized by the same model, indicates that the studied liposome system can be a good surrogate of blood-skin partition.</p> Graphical abstract <p></p>