Determination of acidity constants of sparingly soluble drugs in aqueous solution by the internal standard capillary electrophoresis method

A set of 33 drugs with different solubilities, ranging from soluble to very insoluble, has been chosen in order to evaluate the performance of the internal standard CE method to determine acidity constants of compounds with limited solubility. The set of drugs tested in this work has been chosen as a function of their intrinsic solubility. For the most insoluble compounds, several analytical conditions to overcome the insolubility in aqueous buffers have been tested. This paper assesses the compound solubility limits for the IS-CE method in aqueous pK_a determinations, and also compares the determined pK_as with the results from the literature data obtained by other methods. It is proved that IS-CE method determines acidity constants of sparingly soluble drugs in aqueous media (compounds with logS down to around –6), whereas other reference methods require the use of aqueous–organic solvent buffers and extrapolation procedures to obtain the aqueous pK_a for the same compounds.