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

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 pK values to the several potentially ionizable functional groups was made. The variation of the pK 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 pK values in any of the unlimited number of possible binary solvent acetonitrile-water mixtures, relationships between pK 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 pK values with the solvatochromic parameters of acetonitrile-water mixtures. The equations obtained allow calculation of the pK 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. (C) 1997 Elsevier Science B.V.