Indirect Potentiometric Titration of Sulphamethoxazole in the Presence of Trimethoprim in Co-trimazole Tablets Using Copper Based Mercury Film Electrode

Meeran Mohideen ABDUL KAMAL NAZER, Timiri Khudus SHABEER, Patel RIYAZUDDIN
2001 Chemical and pharmaceutical bulletin  
Sulphamethoxazole [4-amino-N-(5-methyl-3-isoxazolyl)benzene sulphonamide] is widely used in the prevention and cure of bacterial infections. Sulphamethoxazole is mostly marketed in combination with trimethoprim as a co-trimazole dosage form. Assay of sulphamethoxazole in the presence of trimethoprim has drawn considerable attention as evidenced by a number of methods reported, such as spectrophotometry, 1-4) capillary electrophoresis, 5) fluorimetry, 6) calorimetry, 7) nuclear magnetic
more » ... spectrometry 8) and chromatographic methods. 9) Sulphamethoxazole has also been determined by fourier transform infrared spectrometry, 10) atomic absorption spectrometry, 11) voltammetry, 12) oscillographic chronopotentiometry, 13) and visual titrimetry. 14-16) Some of these methods have shortcomings, like poor selectivity and accuracy, or they require expensive equipment. A number of potentiometric methods have been reported, because of their ease of application, simplicity, and speed of analysis. 17-23) Most potentiometric methods use a sulphamethoxazole-selective electrode or other ion-selective electrodes which are either expensive or not readily available in the market, or involve difficult methods of fabrication. Fabrication and application of lab-made inexpensive copper based mercury film electrode (CBMFE) for the potentiometric determination of ascorbic acid and isoniazid have already been reported. 24, 25) In the present communication, a simple and rapid method of indirect titration of sulphamethoxazole, using CBMFE as an indicator electrode, is reported. United States Pharmacopoeia, 26) European Pharmacopoeia, 27) American Pharmaceutical Association Foundation, 28) Indian Pharmacopoeia, 29) and British Pharmacopoeia 30) recommend direct titration of sulphamethoxazole with sodium nitrite in an acidic media at a low temperature. However, this method is not selective, and titrant stability is affected by acidity, temperature, dissolved oxygen and atmospheric carbon dioxide. The proposed method is based on treating sulphamethoxazole with a known excess of silver nitrate and titrating the unreacted silver nitrate against ammo-nium thiocyanate using CBMFE as an indicator electrode. The proposed method is found to be precise, accurate and sensitive. Experimental CBMFE was prepared using a commercially available plastic sleeved copper wire as described in our earlier communications. 24,25) About a 1.0 cm portion of one end of a wire, 1.0 mm in diameter, was polished with emery paper and cleaned with concentrated HNO 3 , after epoxy seal was applied at the junction of the plastic sleeve. The polished wire was coated with mercury by dipping it in mercuric nitrate solution (0.02 M) for 10 min. The electrode surface was wiped with filter paper and then rinsed with water. The titration cell was equipped with CBMFE as an indicator electrode and a double junction calomel electrode containing sodium nitrate solution (0.1 M) in the outer tube. A digital pH/mV meter (precisionϮ1 mV) was used to measure the potentials. A mini magnetic stirrer was used to stir the solution. Reagents All reagents were of analytical grade and deionised distilled water was used to prepare solutions. Stock Solution of Sulphamethoxazole: This solution, containing 1.0-2.0 mg per milliliter, was prepared by dissolving the appropriate amount of sulphamethoxazole in a minimum quantity of 0.1 M NaOH, diluting to a constant volume and standardizing by biamperometric titration against sodium nitrite. 30) Silver Nitrate Solution (0.1 M): This was prepared by dissolving 4.247 g of silver nitrate in 250 ml of water and stored in an amber colored bottle. It was potentiometrically standardized against sodium chloride. 31) Ammonium Thiocyanate (0.1 M): 3.8 g of ammonium thiocyanate was dissolved in 500 ml of water and standardized potentiometrically by titrating with AgNO 3 . 32) Triethanolamine-Nitrate Buffer (pH 8.2): The pH of 0.2 M triethanolamine was adjusted to 8.2 by the addition of 0.05 M nitric acid. Procedure An aliquot containing 1.0-10.0 mg of sulphamethoxazole was taken and the pH was adjusted to 8.2 by the addition of NaOH (0.1 M)/ HNO 3 (0.1 M). One ml of triethanolamine-nitrate buffer (pH 8.2) was added followed by the addition of 1.0-5.0 ml of silver nitrate (0.1 M). A white precipitate of silver-sulphamethoxazole complex appeared shortly thereafter. The solution was diluted to 50 ml with water. The unreacted silver nitrate was titrated against 0.01-0.02 M NH 4 SCN, using CBMFE as an indicator electrode. After each titration, the surface of the electrode was gently wiped with filter paper and rinsed with water. A freshly prepared CBMFE was used for 4-5 titrations. Then, the electrode was renovated by freshly coating it with mercury after cleaning the surface as described.
doi:10.1248/cpb.49.278 pmid:11253916 fatcat:wc3akjdiprh2bmzn5sw6za7wry