ABSTRACT:
Dabigatran is a novel anticoagulant drug acting as a direct and reversible thrombin inhibitor. The purpose of this work was to develop a sensitive and validated LC-MS method for the analysis of Dabigatran etexilate and estimation of its impurity profile in active pharmaceutical ingredient (API) and pharmaceutical dosage forms and to estimate its stability profile according to the ICH guidelines. The method enables to separate 22 impurities appeared in APIs from different resources and Pradaxa® the brand. Forced degradation under stress conditions were carried out in order to establish its stability profile. Dabigatran etexilate was subjected to hydrolysis (acidic and basic), photolysis, thermolysis, and oxidation as per ICH guidelines and found susceptible to all stress conditions. Eleven degradation products were successfully separated, identified and characterized by ESI-MS, then six of them were isolated by semi-preparative HPLC and subjected to NMR spectroscopy and FT-IR to characterize and elucidation of their most possible structures and to predict the possible degradation pathways of Dabigatran etexilate. Comparing Dabigatran etexilate impurity profile and stability profile lead to observe that nine impurities are degradation products resulted by the degradation of dabigatran etexilate, and that defined a considerable overlap can be observed between the impurities and degradation products.