DRUG FORMULATIONS AND CLINICAL METHODS Colorimetric Assay of Cimetidine in the Presence of Its Oxidative Degradates ALAA S. AMIN,HASSAN A. DESSOUKI,SAYED A. SHAMA, and ESLAM A. GOUDA Benha University, Faculty of Science, Chemistry Department, Benha, Egypt Three simple, accurate, and sensitive colorimetric methods for the determination of cimetidine (Cim) in pure form, in dosage forms, and in the presence of its oxidative degradates were developed. These methods are indirect, involve the addition of excess oxidant [N-bromosuccinimide (NBS) for method A; cerric sulfate [Ce(SO 4 ) 2 ] for methods B and C] of known concentration in acid medium to Cim, and the determination of the unreacted oxidant by measurement of the decrease in absorbance of amaranth dye for method A, chromotrope 2R for method B, and rhodamine 6G, for method C at a suitable maximum wavelength, l max : 520, 528, and 525 nm, for the 3 methods, respectively. Regression analysis of the Beer plots showed good correlation in the concentration ranges of 0.2–4.4 mg/mL for method A, and 0.2–3.4 mg/mL for methods B and C. The apparent molar absorptivity, Sandell sensitivity, and detection and quantitation limits were evaluated. The stoichiometric ratio between the drug (Cim) and the oxidant (NBS or Ce 4+ ) was estimated. The validity of the proposed methods was tested by analyzing pure and dosage forms containing Cim with relative standard deviation £1.18. The proposed methods could successfully determine the studied drug with varying excess of its oxidative degradation products, with recovery between 99.2 and 101.8, 100.2 and 102.8, and 99.8 and 102.0% for methods A–C, respectively. C imetidine, 2-cyano-1-methyl-3-[2-[[(5-methyl imidazole- 4-yl)methyl]thio] ethyl] guanidine (CAS 51481-61-9), is an effective histamine H 2 -receptor antagonist which inhibits the secretion of basal and gastric acid and reduces the output of pepsin. The drug is extensively used in the treatment of duodenal and gastric ulcers, in the management of reflux esophagitis, and for the inhibition of gastric acid secretion associated with Zollinger-Ellison Syndrome (1–3). It is excreted as the unchanged drug (56–85%) and as hydroxymethyl, sulfoxide, or guanylurea metabolites (4). Several methods have been reported for determination of cimetidine (Cim), including chromatography (5–8), polarography (9–11), voltammetry (12), electrophoresis (13, 14), titrimetry (15–17), spectrofluorimetry (18), and spectrophotometry (19–29). Emphasis has been given to spectrophotometric and titrimetric methods, because they are simple and easily manageable. The volumetric titrations are performed by some oxidants via 0.1 N-bromate–bromide solution, (0.02 N); N-bromosuccinimide (NBS); and (0.01 M) N,N¢-dibromodimethylhydantoin (DBH) for the methods described in references 14–16, respectively. All these methods determine Cim in the concentration range of 3.0–9.0 mg/mL. The spectrophotometric methods also suffer from disadvantages such as long reaction time (³30 min) for color development (19–26), requirement for prior extraction of the colored product (21), low sensitivity and inability to accurately analyze solutions containing <50 mg/mL (20, 23, 25, 27, 28), and low stability of colored species (<15 min; 25). The UV-spectrophotometric method (29), as well as all of these spectrophotometric methods, cannot determine concentration of Cim <1.0 mg/mL. This paper describes 3 colorimetric methods, which are superior to the reported ones, for their selectivity and high sensitivity. The British Pharmacopoeia prescribes nonaqueous titration of the sample solution using 0.1 M HClO 4 as titrant, and the end point is detected potentiometrically (30). The present work aims to demonstrate simple, rapid, accurate, sensitive, and selective colorimetric methods suitable and convenient for the determination of Cim in pure form, in dosage forms, and in the presence of its oxidative degradates. Experimental Apparatus All the absorption spectral measurements were made using JASCO V-530 (UV-Vis) spectrophotometer (JASCO, Tokyo, Japan) equipped with 10 mm matched quartz cells, a scanning speed of 400 nm/min, and a band width of 2.0 nm. Material and Reagents All chemicals used were of analytical or pharmaceutical grade purity, and water was doubly distilled. Pure Cim was provided by Kahira Pharmaceutical and Chemical Industries 382 AMIN ET AL.: JOURNAL OF AOAC INTERNATIONAL VOL. 92, NO. 2, 2009 Received March 12, 2008. Accepted by SW June 1, 2008. Corresponding author’s e-mail: asamin2002@hotmail.com