Protonation equilibria of quinolone antibacterials in acetonitrile-water mobile phases used in LC

Abstract

Ionization constants of nine quinolone antibacterials in acetonitrile-water mixtures containing 0, 5.5, 10, 16.3, 25, 30, 40, 50 and 70% (w/w) acetonitrile were obtained and assignment of these p K values to the several potentially ionizable functional groups was made. The variation of the p K values obtained over the whole composition range studied can be explained by consideration of the preferential solvation of electrolytes in acetonitrile-water mixtures. In order to obtain p K values in any of the unlimited number of possible binary solvent acetonitrile-water mixtures, relationships between p K values and different bulk properties (such as dielectric constant) were examined. The linear solvation energy relationships method, LSER, was applied to study the correlation of p K values with the solvatochromic parameters of acetonitrile-water mixtures. The equations obtained allow calculation of the p K values of the quinolone antimicrobials in any acetonitrile-water mixtures up to 70% (w/w) and thus permit the knowledge of the acid-base behaviour of these important antimicrobials in the widely used acetonitrile-water media.