A method is presented for the determination of sulphacetamide sodium, sulphadimidine and sulphathiourea in the presence of their acid-induced degradation products using first derivative spectrophotometry. By measuring the absolute value of the first derivative curves at the zero contribution of the corresponding degradation products, the concentration of the intact drug can be calculated directly without interference of the degradation product. The validity of the method was confirmed using synthetic mixtures of the intact drugs with their degradation products.