Sulphonamide drugs (sulphamethazine, sulphamerazine, sulphadiazine, sulphathiazole) were studied in a wide potential window (between 2 and − 2 V) in acetonitrile, dimethyl sulphoxide and in 50–50 v/v% binary mixtures of acetonitrile and water. The voltammograms of the outlined compounds were very similar both in the anodic and cathodic part in each non-aqueous solvents except for sulphathiazole. These sulphonamide drugs were also investigated in presence of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) and its sodium salt and the voltammograms changed due to an acid–base reaction. HEPES and its sodium salt could be investigated in acetonitrile only in their saturation concentration as they were slightly soluble in this solvent. In a separate experiment their solubilities were determined at 298 K in acetonitrile with the co-solvent calibration method using water as co-solvent. Complementary fluorescence studies in dimethyl sulphoxide did not show the presence of any interaction between sulphonamide drugs and HEPES as well as its sodium salt.