NOVEL METHOD FOR SEPARATION AND QUANTIFICATION OF POTENTIAL IMPURITIES BY RP-HPLC FROM KSM STAGE TO API STAGE OF DABIGATRAN MESYLATE

Dabigatran mesylate is a novel oral anticoagulant that works by blocking the clotting protein thrombin. The present work describes the separation and quantification of potential impurities in a single HPLC method, which are generated from raw materials to API synthesis. This method is capable of separating and quantifying the fourteen impurities, produced from the intermediate stages to final drug substance stage of dabigatran within 40 min of run time. Column: Poroshell 120, EC C-18, 150 mm × 4.6 mm, 2.7 µ; Buffer: 2.04 g of Potassium dihydrogen phosphate in a beaker, add 1500 mL of water and dissolve, to this add 1.5 ml Triethylamine (TEA) and 1 ml of Phosphoric acid; Diluent: water and acetonitrile in the ratio 20:80% v/v; The flow rate: 0.7 mL/min; Column temperature: 40 °C. Wavelength: 230 nm; The drug substance was subjected to stress studies such as hydrolysis, oxidation and thermal degradation and considerable degradation was observed in acidic hydrolysis and oxidative stress conditions. The formed degradation products were well-resolved from the dabigatran drug substance and its related impurities. The validated method produced good results of precision, linearity, accuracy, robustness and ruggedness. The proposed method was found to be suitable precise, sensitive and accurate for the quantitative determination of related impurities in the samples of Dabigatran mesylate drug substance.