Simultaneous spectrophotometric determination of trimethoprim and sulphamethoxazole following charge-transfer complexation with chloranilic acid

AbstractA simple, accurate and precise simultaneous spectrophotometric method has been developed for the analysis of trimethoprim–sulphamethoxazole combination in pure and tablet dosage forms. The method involves direct charge transfer complexation of trimethoprim (TMP) with chloranilic acid (CAA) in acetonitrile–dioxane solvent mixture and complexation of sulphamethoxazole (SMZ) after its hydrolysis in dilute H2SO4. Optimization of temperature and time revealed the superiority of room temperature and 20 and 30min respectively for TMP and SMZ. Optimal detector responses were obtained at 520 and 440nm and were therefore selected as working wavelength maxima for SMZ and TMP respectively. TMP and hydrolysed SMZ were combined with CAA at mole ratios of 1:1 and 1:3 respectively. Accuracies were generally less than 4% (estimated as degree of inaccuracy or error) with a precision of the order of less than 2% on a three-day assessment. Physicochemical factors responsible for complex stability were estimated and related to the observed data. The method was successfully applied to the determination of TMP and SMZ in tablet dosage forms with accuracies comparable to the official BP method. There were no interferences from common tablet excipients and TMP complex did not interfere with the assay of SMZ. The developed method could find application in routine quality control of TMP–SMZ combination. It is the first reported full simultaneous colorimetric assay of TMP and SMZ using the same analytical reagent