Determination of the dissociation constant of a weak acid using a dissolution rate method

Based on theories of diffusion-controlled mass transport for dissolution processes of weak acids in aqueous alkaline media, a method for the determination of the dissociation constant of a weak monoprotic acid is described. The method includes measurements of the initial dissolution rate as a function of pH, using the rotating-disk technique, and determination of the intrinsic solubility. The method was applied to determine the apparent dissociation constant (mu = 0.1) of 5,5-dimethyl-3-(alpha,alpha,alpha,4-tetrafluoro-m-tolyl)hydantoin, a new schistosomicide. For comparison, a spectrophotometric method for the pKa determination was developed. Due to rapid hydrolysis of the compound in the pH range required for the determination of the pKa, the development of the latter method turned out to be complicated and tedious. The results of both methods were in good agreement. For compounds with unfavorable properties for titrimetric or spectrophotometric determination of the pKa value, the dissolution rate method can be a useful alternative.