Ionic Partition Diagrams:  A Potential−pH Representation

A general method to predict and interpret the transfer mechanisms of ionizable compounds at the interface between two immiscible electrolyte solutions (ITIES) is presented. The approach is based on the construction of the ionic partition diagram of the solute. It consists in defining equiconcentration boundaries as a function of the Galvani potential difference and aqueous pH by taking into account the thermodynamic equilibria governing the distribution of the various acid/base forms of the molecules involved. The method defines the domains of predominance of each species either in the aqueous or in the organic phase. The application of ionic partition diagrams to quinidine offers a global and direct visualization of all the species and demonstrates the validity and efficiency of the method in helping to understand the transfer and partition mechanisms of ionizable drugs.