Nitro derivatives of five-membered heterocyles are of considerable interest. Some are biologically active with anti-inflammatory or vasodilatory activity (1). The 5-nitroimidazoles are used as antiamoebic, antiprotozoal and antibacterial agents. Two important members of this chemical class are metronidazole and tinidazole. Discovery of the anti-trichomonal properties of metronidazole revolutionized the treatment of disease. A new approach to the spectrophotometric determination of metronidazole (MZ) and tinidazole (TZ) has been developed. The procedure involves coupling of diazotized nitroimidazoles with p-dimethylaminobenzaldehyde (DMAB) to form a greenish-yellow solution. Optimal temperature and time were 0°C (iced) and 3 minutes for diazotization and 30°C and 2 minutes for coupling for both MZ and TZ. Coloured adducts of MZ and TZ showed shoulders at 406 nm and 404 nm, respectively, which were selected as analytical wavelengths. The reaction with p-DMAB occurred in a 1:1 mole ratio. Beer's law was obeyed within the 4.8-76.8 mg mL -1 concentration range with low limits of detection. The azo adducts were stable for over a week. Molar absorptivities were 1.101 0 3 (MZ) and 1.30´10 3 L mol -1 cm -1 (TZ). Overall recoveries of MZ and TZ from quality control samples were 103.2 ± 1.3 and 101.9 ± 1.3 % over three days. There was no interference from commonly utilized tablet excipients. No significant difference was obtained between the results of the new method and the BP titrimetric procedures. The azo approach using the p-dimethylaminobenzaldehyde procedure described in this paper is simple, fast, accurate and precise. It is the first application of DMAB as a coupling component in the diazo coupling reaction.
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.
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