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

Abstract

A 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 H 2 SO 4 . Optimization of temperature and time revealed the superiority of room temperature and 20 and 30 min respectively for TMP and SMZ. Optimal detector responses were obtained at 520 and 440 nm 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.

Optimization, Validation and Application of UV-Vis Spectrophotometric-Colorimetric Methods for Determination of Trimethoprim in Different Medicinal Products

“…Charge transfer complexation reactions have been widely applied in quality control of important chemical compounds of pharmaceutical interest in human and veterinary medicine, as well (5,8,15). For the methods we proposed, there were insufficient validation or applicability data on various real formulation forms (5,15).…”

“…Other more rarely reported methods for TMP determination are titrimetric (16), voltametric (17), polarographic (18). Even though the Official pharmacopeia method includes HPLC determination (19), still, there are numerous UVVis methods proven as satisfactory alternative to the liquid chromatography (3,8,10,11,15). The main advantage thereof is their simplicity, rapidity, and low cost-effectiveness.…”

“…formulations, are based on direct (7,9,10) and colorimetric spectrophotometry (5,8,15). Regarding the colorimetric spectrophotometry, the first publication (5), describes application of several reagents as π-acceptors for obtaining adduct products: bromothymol blue, bromocresol green, and alizarin red S. As extraction solvents the authors have proposed chloroform, methylene chloride and chlorobenzene.…”

“…Regarding the colorimetric spectrophotometry, the first publication (5), describes application of several reagents as π-acceptors for obtaining adduct products: bromothymol blue, bromocresol green, and alizarin red S. As extraction solvents the authors have proposed chloroform, methylene chloride and chlorobenzene. Adekoge et al (8) have developed a method for spectrophotometric determination of TMP following charge-transfer complexation with chloranilic acid. The published study by Al-Sabha et al (15), describes spectrophotometric determination of TMP based on the reaction of the amine group with 2,4-dinitro-1-fluorobenzene (DNFB) reagent in acetone medium.…”

“…Such methods include different analytical techniques mostly ultraviolet and visible (UV-Vis) spectrophotometry (3,(5)(6)(7)(8), derivative spectrophotometry (9)(10)(11), high performance liquid chromatography (HPLC) (12)(13)(14) and chemometric methods applying multivariate calibrations (7). Other more rarely reported methods for TMP determination are titrimetric (16), voltametric (17), polarographic (18).…”