Evaluation of Liposome−Water Partitioning of Organic Acids and Bases. 2. Comparison of Experimental Determination Methods

Abstract

The experimental determination of liposome−water partition coefficients, Klipw, of the neutral and charged species of ionogenic compounds is rather tedious because apparent distribution ratios have to be measured as a function of pH and ionic strength. The partition coefficients of the single species have to be extrapolated from the experimental data using an appropriate partition model. A number of new assay methods have been developed in the past years to facilitate and speed up the experimental procedure for the determination of Klipw. Here we compare three proposed assay methods with the well-established equilibrium dialysis method, and we evaluate their applicability for ionogenic compounds. The potentiometric method was initially developed for the determination of octanol−water partitioning but was recently extended to liposome−water partitioning. The potentiometric method described here was found to yield satisfactory estimates of the Klipw-values of both neutral and charged species, although manif...