Development and Validation of Stability-indicating Rp-hplc Assay Method for Entacapone in Entacapone Tablets

A new, simple, precise, rapid, accurate and stability-indicating RP-HPLC method has been developed for the determination of Entacapone in presence of its degradation products or other pharmaceutical excipients. Stress studies were performed on Entacapone tablets and it was found that it degrades sufficiently in acidic, alkaline and oxidation conditions, while negligible degradation was observed in thermal, photolytic and humidity conditions. The peaks of the degradation products were not observed in the chromatogram due to the nonchromophoric nature of the degradation moiety formed. The separations were carried out on a Hypersil BDS C8, 150 mm x 4.6 mm 5μm particle size column with a mobile phase consisting of Acetonitrile: 0.01% Orthophosphoric acid pH 2.5 at a flow rate of 1.0 ml/min. Detection wavelength was 210nm. The retention time of Entacapone was 7.0minutes. The developed method was validated in terms of specificity, forced degradation, linearity, precision, intermediate precision (ruggedness), accuracy, range and robustness. The calibration curve for Entacapone was linear (correlation coefficient 0.99995) from range of 50μg/ml to 150μg/ml. Relative standard deviation values for all the key parameters was less than 2.0%. The recovery of the Entacapone was found to be 100.3%. Thus, the developed RP-HPLC method was found to be suitable for the determination of Entacapone in bulk as well as stability samples of the pharmaceutical dosage forms containing various excipients. INTRODUCTION: Entacapone is a selective, reversible catechol-O-methyl transferase (COMT) inhibitor for the treatment of Parkinson’s disease. It is a member of the class of nitrocatechols. When administered concomitantly with levodopa and a decarboxylase inhibitor (e.g., carbidopa), increased and more sustained plasma levodopa concentrations are reached as compared to the administration of levodopa and a decarboxylase inhibitor 1, 2, . Chemically it is (2E)-2-cyano-3-(3,4-dihydroxy-5nitrophenyl)-N,N-diethyl prop-2-enamide. Greenish yellow to yellow powder, sparingly soluble in acetone and in methanol, slightly soluble in ethanol, very slightly soluble toluene, practically insoluble in water 4, 5, . Stability screening of drug candidates constitutes an inevitable part of drug discovery. The need for the stability studies on a drug candidate arises from the fact that the chemical integrity of the drug substance should be maintained until the compound is delivered to the intended site of action.