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Utility of N-Bromosuccinimide for the Titrimetric and Spectrophotometric Determination of Famotidine in Pharmaceutical Formulations

DOI: 10.1155/2011/581372

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Abstract:

Two titrimetric and two spectrophotometric methods are described for the assay of famotidine (FMT) in tablets using N-bromosuccinimide (NBS). The first titrimetric method is direct in which FMT is titrated directly with NBS in HCl medium using methyl orange as indicator (method A). The remaining three methods are indirect in which the unreacted NBS is determined after the complete reaction between FMT and NBS by iodometric back titration (method B) or by reacting with a fixed amount of either indigo carmine (method C) or neutral red (method D). The method A and method B are applicable over the range of 2–9?mg and 1–7?mg, respectively. In spectrophotometric methods, Beer's law is obeyed over the concentration ranges of 0.75–6.0? g? (method C) and 0.3–3.0? g? (method D). The applicability of the developed methods was demonstrated by the determination of FMT in pure drug as well as in tablets. 1. Introduction Famotidine (FMT), 3-[2-(diaminomethyleneamino)thiazol-4-ylmethylthio]-N-sulfamoylpropionamidine (Figure 1), is a histamine H2-receptor antagonist (H2-RA). It is widely used for the treatment of duodenal ulcers, benign gastric ulcer, reflux oesophagitis, and hyperacid secretory conditions. FMT is official in both the British Pharmacopoeia (BP) [1] and the United States Pharmacopoeia (USP) [2]. The BP [1] recommends thin-layer chromatography using a silica gel F254 precoated plate (Fischer Silica Gel GF plates are suitable) and a mixture of 2 volumes of 13.5?M ammonia, 20 volumes of toluene, 25 volumes of methanol, and 40 volumes of ethyl acetate as the mobile phase. The USP [2] recommends a potentiometric nonaqueous method for the determination of FMT using perchloric acid as the titrant and a HPLC method using a mixture of acetate buffer of pH 6?:?acetonitrile (93?:?7) as a mobile phase with UV detection at 275?nm. Figure 1: Structure of famotidine. Several procedures have been reported in the literature for the analysis of FMT. The reported methods include HPLC [3–5], HPTLC [6, 7], capillary electrophoresis [8], potentiometry [9], differential pulse voltammetry [10], spectrofluorimetry [11, 12], polarography [13], and UV-spectrophotometry [14]. Some of these methods involve several manipulation steps, which are not simple for routine analysis of pharmaceutical formulations and need sophisticated instruments. Titrimetry and visible spectrophotometry may serve as useful alternatives to many of the aforesaid sophisticated techniques because of their cost effectiveness, ease of operation, sensitivity, remarkable accuracy and precision, and wide

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