Titrimetric and Spectrophotometric Methods for the Assay of Ketotifen Using Cerium(IV) and Two Reagents

One titrimetric and two spectrophotometric methods are described for the determination of ketotifen fumarate (KTF) in bulk drug and in tablets using cerium(IV) as the oxidimetric agent. In titrimetry (method A), the drug was treated with a measured excess of cerium(IV) in H2SO4 medium and after a standing time of 10 min, the surplus oxidant was determined by back titration with iron(II). The spectrophotometric procedures involve addition of a known excess of cerium(IV) to KTF in acid medium followed by the determination of unreacted oxidant by reacting with either p-dimethyl amino benzaldehyde and measuring the resulting colour at 460？nm (method B) or o-dianisidine and subsequent measurement of the absorbance of coloured product at 470？nm (method C). Titrimetric assay is based on a 1？:？2 reaction stoichiometry between KTF and cerium(IV) and the method is applicable over 2–18？mg range. In spectrophotometry, regression analysis of Beer’s law plots showed a good correlation in 0.4–8.0 and 0.4–10.0？g？mL？1 KTF ranges for method B and method C, respectively, and the corresponding molar absorptivity coefficients are calculated to be and ？L？mol？1？cm？1. 1. Introduction Ketotifen fumarate (KTF) (Figure 1), chemically known as 4,9-dihydro-4-(1-methyl-4-piperidinylidene)-10H-benzo cyclohepta-[1,2-b] thiophen-10-one, which belongs to the group of cyclohepta thiophenones is an antiallergic drug with stabilizing action on mast cells, analogous to that of sodium cromoglycate, and anti-H1 effect [1]. Ketotifen is given orally as fumarate in the prophylactic management of asthma and is used in the treatment of allergic conditions such as rhinitis and conjunctivitis [2]. Ketotifen is a nonbronchodilator, antiallergic properties, and has a specific anti-H1 effect [3]. Figure 1: Structure of KTF. The drug is official in British Pharmacopoeia [4], which describes a potentiometric titration with perchloric acid in acetic anhydride-acetic acid medium. The therapeutic importance of the drug has prompted the development of a variety of techniques for its assay in pharmaceuticals and body fluids. In pharmaceuticals, it is quantified by high performance liquid chromatography [4–10], high performance thin layer chromatography [11], liquid chromatography with tandem mass spectrometry [12], capillary electrophoresis [13], spectrofluorimetry [14], direct differential pulse polarographic and adsorptive-stripping voltammetry [15], and UV spectrophotometry [16, 17]. Potentiometric titration methods employing polymeric membrane sensors were also developed, where the method involved