Membrane activity of ionisable drugs - a task for liquid-liquid electrochemistry?

Structurally related aminoacridine therapeutics (aminacrine, tacrine, velnacrine and proflavine) were studied electrochemically at the interface between two immiscible electrolyte solutions. To assess both their neutral and ionic partition coefficients, cyclic voltammetry was used to obtain the transfer potential as a function of the aqueous phase pH. Subsequently, in order to create a simple model of a biological membrane, a lipid monolayer was deposited at the liquid-liquid interface using the Langmuir-Blodgett technique. Electrochemical impedance spectroscopy was employed to study the interactions between the drug ions and the biomimetic phospholipid monolayer. Using a model incorporating a charge transfer mechanism coupled with potential dependent adsorption steps, the membrane activity of the studied drug ions could be estimated. The results indicate liquid-liquid electrochemistry to be a versatile tool for detecting differences in membrane activity even between structurally very similar drugs. (C) 2003 Elsevier Science B.V. All rights reserved.