Electroreduction of the Muscle Relaxant Drug Dantrolene Sodium at the Mercury Electrode and Its Determination in Bulk Form and Pharmaceutical Formulation

Abstract

Dantrolene sodium (Chart 1) is the hemihepta hydrate of sodium salt of 1-[5-(4-nitrophenyl)furfulidene amino]imidazolidene-2,4-dione. It is a muscle relaxant reported to act by blocking muscle concentration beyond the neuromuscular junction.1) It is described for the symptomatic relief of muscular spasm due to condition such as stroke, multiple sclerosis, spinal cord injury and cerebral palsy. Dantrolene sodium is used also intravenously in the treatment of malignant hyperthermia. 1)Only few liquid chromatographic methods 2-8) were described for assay of dantrolene sodium in dosage form and biological fluids. The chromatographic methods usually necessitate sample pretreatment and time-consuming extraction steps prior to analysis of the drug. Moreover, these methods required expensive equipment and considerable skills are necessary to operate them successfully. Although no official analytical method for determination of dantrolene sodium is reported in British or the United States pharmacopoeia an official electrometric titration method for determination of the drug is available in the Japanese pharmacopoeia. Besides, no any information is available in the literature to date concerning the electroreduction of dantrolene sodium or its electroanalytical determination. Therefore, the present work aimed to study the electroreduction pathway of dantrolene sodium at the mercury electrode and to describe simple and precise electroanalytical procedures for its determination in bulk form and pharmaceutical formulation. ExperimentalInstrumentation A Sargent-Welech Polarograph Model 4001 (Fisher, U.S.A.) was used for the present polarographic measurements. The electrolysis cell was as that previously described by Meites. 9) Characteristics of the capillary of the dropping mercury electrode (DME) were: mϭ1.13 mg/s and tϭ3.36 s in a solution of 0.1 M KCl at open circuit conditions for a mercury height of 60 cm. A saturated calomel electrode was used as a reference electrode.Computer-controlled Electrochemical Analyzers Models 273A and 363A-PAR (Princeton Applied Research, Oak Ridge, TN, U.S.A.) controlled via 270/250-PAR software were used for the voltammetric measurements. An electrode assembly (303A-PAR) incorporated with a three-electrode configuration system comprising of a hanging mercury drop electrode (HMDE) or a dropping mercury electrode (DME) as a working electrode (surface areaϭ0.026 cm 2 ), an Ag/AgCl/KCl s reference electrode and a platinum wire auxiliary electrode, was used. A magnetic stirrer (305-PAR) and a stirring bar were used to provide the convective transport during the accumulation step.A potentiostat/galvanostat (Model 173-PAR) incorporated with a digital coulometer Model 179-PAR was used for controlled-potential electrolysis of dantrolene sodium solutions. The coulometric cell used was designed by Princeton Applied Research (PAR) Corporation to have a large electrode surface area to solution volume ratio as possible. A mercury pool as a working electrode, a saturated calomel electrode as a reference a...

Protein-film voltammetry: A theoretical study of the temperature effect using square-wave voltammetry

“…The features of the SW voltammograms presented in Fig. 7 should avoid the dangers of invoking multiple species, "stable radicals", or additional processes to explain "odd" features met in some studies, such as appearance of multiple peaks or very narrow peaks [24][25][26][27][28][29][30][31][32][33], particularly in SW voltammetric studies performed under cryogenic conditions.…”

Comparison Study of Voltammetric Behavior of Muscle Relaxant Dantrolene Sodium on Silver Solid Amalgam and Bismuth Film Electrodes

“…DAN voltammetric behavior on mercury electrodes was described in [ 47 – 49 ]. Cox et al [ 47 ] applied DPP with dropping mercury electrode (LOD 3.0 × 10 −7 mol L −1 ).…”

“…Similar method was presented by C. S. Reddy and S. J. Reddy [ 48 ] (LOD 8.0 × 10 −8 mol L −1 ). Other authors applied various polarographic and voltammetric techniques and the lowest LOD obtained using adsorptive stripping square wave voltammetry (AdS SWV) (2.1 × 10 −10 mol L −1 ) [ 49 ]. These papers describe the reduction of DAN via the reduction of the present nitro group (−0.25 V and −0.50 V versus SCE) and reduction of the azomethine group (−0.85 V) in acidic medium.…”

“…These papers describe the reduction of DAN via the reduction of the present nitro group (−0.25 V and −0.50 V versus SCE) and reduction of the azomethine group (−0.85 V) in acidic medium. In alkaline medium, only the first cathodic signal corresponding to the reduction of –NO 2 group can be observed [ 47 – 49 ]. DPP was also applied for study of physicochemical properties of DAN, especially for the determination of its p K a value [ 50 ].…”

Stability-Indicating Chromatographic Methods for the Determination of a Skeletal Muscle Relaxant and an Analgesic in their Combined Dosage Form

“…Literature review revealed that several electrochemical methods [4][5][6] and HPLC methods [7][8][9][10][11][12][13][14] have been reported for the determination of DNT either in pharmaceutical or biological samples. Degradation behavior of DNT was reported in different buffers and temperature [15].…”