The potential of using CE frontal analysis (CE-FA) to study the interactions between a range of charged low molecular weight drug substances and liposomes was evaluated. The liposomes used were net negatively charged and consisted of 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-phosphate monosodium salt in a ratio of 80/20 mol%. Apparent distribution coefficients (D-mem), defined as the molar concentration of drug substance in the membrane phase divided by the molar concentration of drug substance in the aqueous phase, were successfully determined for six positively and eight negatively charged drug substances with log D-mem ranging from 1.35 to 3.63. The extent of hposome-buffer distribution was found to be dependent on the drug concentration. The results obtained with the developed CE-FA method were in good agreement with results obtained by equilibrium dialysis. Furthermore, the CE-FA method was faster, less labor intensive and required smaller sample volumes (similar to 50 mu L) compared with equilibrium dialysis. Thus, CE-FA is an efficient and useful tool for the characterization of interactions between liposomes and low molecular weight drug substances.