Evaluation of liposome-water partitioning of organic acids and bases. 2. Comparison of experimental determination methods

The experimental determination of liposome-water partition coefficients, K- lipw, of the neutral and charged species of ionogenic compounds is rather t edious because apparent distribution ratios have to be measured as a functi on of pH and ionic strength. The partition coefficients of the single speci es have to be extrapolated from the experimental data using an appropriate partition model. A number of new assay methods have been developed in the p ast years to facilitate and speed up the experimental procedure for the det ermination of K-lipw,. Here we compare three proposed assay methods with th e well-established equilibrium dialysis method, and we evaluate their appli cability for ionogenic compounds. The potentiometric method was initially d eveloped for the determination of octanol-water partitioning but was recent ly extended to liposome-water partitioning. The potentiometric method descr ibed here was found to yield satisfactory estimates of the K-lipw-values of both neutral and charged species, although manifestation of electrostatic saturation phenomena cannot be fully ruled out due to the relatively high c oncentrations of compounds that have to be used. Two further methods based on immobilization of lipid material on a solid support, which were initiall y developed for the estimation of K-lipw,, of neutral compounds, were teste d here for their applicability to charged organic species. IAM (immobilized artificial membrane) chromatography was found not to he suitable for predi ction of membrane-water partitioning of ionic compounds because the charges on the chromatographic support material are not sufficiently shielded. A m odel including free silica and free amine sites explained the experimental data very well. A new type of immobilized liposomes in the form of noncoval ently coated large porous particles (TRANSIL) gave promising results with K -lipw-values that agree well with those determined with the traditional equ ilibrium dialysis method. The advent of these alternative methods for the d etermination of K-lipw of ionogenic compounds will facilitate the applicati on of K-lipw as a descriptor for biological systems in quantitative structu re activity relationships in environmental chemistry and toxicology.