0039.9140186 $3.00 +000 Pergamon Press Ltd zyxwvu A RAPID METHOD FOR THE DETERMINATION OF SOME ANTIHYPERTENSIVE AND ANTIPYRETIC DRUGS BY THERMOMETRIC TITRIMETRY U. M. ABBASI and FATEH CHAND Department of Analytical Chemistry, Institute of Chemistry University of Sind, Jamshoro, Sind, Pakistan M. I. BHANGER and S. A. MEMON National Centre of Excellence in Analytical Chemistry, University of Sind, Jamshoro, Sind, Pakistan zyxwvutsrqpon (Received 6 September 1983. Revised 21 August 1985. Accepted 25 September 1985) Summary-A simple and rapid method is described for the direct thermometric determination of milligram amounts of methyl dopa, propranolol hydrochloride, I-phenyl-3-methylpyrazolone (MPP) and 2,3-dimethyl-I-phenylpyrazol-S-one (phenazone) in the presence of excipients. The compounds are reacted with N-bromosuccinimide and the heat of reaction is used to determine the end-point of the titration. The time required is approximately 2 min, and the accuracy is analytically acceptable. N-Bromosuccinimide (NBS) is a valuable reagent for the determination of many organic compounds.’ Its use as a titrant for the determination of ascorbic acid was first introduced by Barakat et al.’ Pathak et al.’ have reported the titration of methyl dopa and propranolol hydrochloride with NBS, with Methyl Red as indicator. Potentiometric titration of pharma- ceuticals with NBS is also reported in the literature.4.5 The usefulness of NBS results from its high oxidation potential and applicability in oxidation, substitution and addition reactions.2,6 In analysis of pharmaceuticals problems sometimes arise if the matrix is coloured or the components of the formulation are not all readily soluble in the reaction medium. The classical methods of analysis therefore often involve a filtration or solvent extrac- tion step before the active ingredient is in a suitable medium for determination. Thermometric titrimetry overcomes this problem provided the reaction chosen is selective for the active ingredient, the heat of reaction is large enough, and the excipients are thermally neutral. By taking advantage of the rapid bromination reaction of NBS with organic com- pounds, we have developed a simple, fast and selec- tive thermometric method which is quantitive and accurate for the determination of milligram amounts of some antihypertensive and antipyretic drugs. EXPERIMENTAL Insrrumentation and procedure The instrument was as described earlier,’ with certain modifications. The basic electrical circuit had a simple d.c. Wheatstone bridge, incorporating a thermistor of nominal resistance 10 kR at 25” (Standard Telephone and Cables Ltd., model F-14). The off-balance voltage was fed into an operational amplifier and the output recorded (2-mV full- scale deflection) at a chart-speed of 6 cm/min. For accurate and precise delivery of the titrant and titrand a Mettler automatic titrator model DV 11 or 13 was coupled with the instrument. The delivery rate was found gravimet- rically to be 4.47 ml/min. The titrant was maintained at a constant temperature of 24.00 + 0.01” by passage through a thermostat before entering the titration vessel. The titration vessel was a thick-wailed polythene bottle of nominal capac- ity 15 ml, and was thermally insulated m a polystyrene block so that heat losses during titration were not significant. A known amount of sample was placed in the titration vessel and stirred mechanically at constant speed until thermal stability was achieved. It was then titrated with NBS and the amount of sample estimated from the enthalpogram. Reagents The methyl dopa (Merck, Sharp and Dohme) and pro- pranolol hydrochloride (Ciba-Geigy) used were of pure pharmaceutical grade. The phenazone and MPP were pre- pared by a standard pr0cedure.s The identity and purity of all these reagents were checked by taking melting points and mixed melting points, followed by ultraviolet spectroscopy’,” thin-layer chromatography, and analysis by a standard method.” Standard solutions (100 ml) were prepared by dissolving accurately weighed amounts in doubly distilled water. The NBS was standardized io- dometrically.’ RESULTS AND DISCUSSION Methyl dopa, propranolol hydrochloride, phen- azone and MPP were thermometrically titrated with standard NBS solution. The results obtained (Table 1) were precise and accurate with relative standard deviations in the range 0.34.6%. The chemical structures of these compounds are given below. Various matrix ingredients such as starch, lactose and magnesium stearate, frequently used in pharmaceutical preparations, were found to have no effect on the determinations. Hence single-dosage forms can be analysed. All these data suggest that the test compounds are brominated readily and quan- titatively. 173