Potentiometric determination of pKa of some selected antibiotics in mixed solvent media

Abstract

The ionization constants of some selected antibiotics namely sulfamethoxazole, trimethoprim and metronidazole have been determined by potentiometry in some mixed solvent media by varying the concentrations at 25^oC. The ionization constants varied with the proportion and nature of different solvent mixtures used, as most exhibited their highest pKa values in 100% DMSO. Specifically, it has been found that in MeOH-DMSO mixture as the proportion of methanol increases, there is reduction in the pKa values for all the antibiotics. In all the solvent mixtures, the pKa values of 7.92, 8.29, 7.61, 7.98, 7.78 (trimethoprim) and 2.99, 2.87, 2.58 and 2.97 (metronidazole) obtained are higher than the reported values at physiological pH for trimethoprim and metronidazole. However, the pKa values obtained for sulfamethoxazole are comparable to the equilibrium dissociation of its amine moiety.

Keywords: Antibiotics, pKa values, mixed solvent, drug permeability, ionization constants