Kinetic spectrophotometric methods for determination of trimetazidine dihydrochloride

Four simple and sensitive kinetic spectrophotometric methods (I-IV) for the determination of trimetazidine dihydrochloride (TRMZ) have been developed. Method I was based on the oxidation of the drug with alkaline KMnO4 producing green manganate species. Method II was based on the formation of colored condensation product between TRMZ and 4-chloro-7-nitrobenzofurazan (NBD-Cl). Method III was based on reaction of TRMZ and with 1,2-naphthoquinone-4-sulphonic acid sodium salt (NQS) forming orange colored product. Method IV was based on the formation of a violet charge-transfer complex between trimetazidine base and p-chloranil (pCL). These reactions were followed spectrophotometrically by measuring the rate of color development at 610, 475, 485 and 560 nm for the reactions with KMnO4, NBD-Cl, NQS, and pCL, respectively. The variables affecting the reactions were carefully investigated and the conditions were optimized. The stoichiometries of the reactions were determined, and the reactions pathways were postulated. The initial rate and fixed time methods were utilized for constructing the calibration graphs for the determination of TRMZ concentration. The assays limits of detection were 0.2-2.5 μg ml−1. The analytical performance of the methods, in terms of accuracy and precision, were statistically validated; the results were satisfactory. The methods have been successfully applied to the determination of TRMZ in commercial pharmaceutical formulations. Statistical comparison of the results with the reference method showed excellent agreement and proved that no significant difference in the accuracy and precision.