The purpose of this study was to determine the ionisation constants of two poorly soluble compounds, namely diphacinone and chlorophacinone, potentiometrically in 1,4-dioxane-water mixtures with ibuprofen used as a standard. In this study, Gran's method was employed for the calibration of glass electrode in cosolvent systems with pH measurements based on the concentration scale (p(c)H). Aqueous pK(a) values for the tested compounds were obtained by extrapolation on a Yasuda-Shedlovsky plot. It was demonstrated that the pK(a) for ibuprofen determined using this method was consistent with those reported in literature. The technique was applied successfully to the two indandione derivatives, diphacinone and chlorophacinone. The present study demonstrated that the use of an organic cosolvent is effective in improving the solubility of compounds allowing potentiometric determination of ionisation constants that are otherwise difficult in aqueous solutions.
