The Methodological Study Of The Related Substances Of Dabigatran Etexilate Mesylate

Dabigatran etexilate,which can prevent venous thrombosis in adult patients undergoing selective total knee and total hip arthroplasty,as well as reduce stroke and systemic embolic risk in patients with non-valvular atrial fibrillation(NVAF),is a direct thrombin inhibitor manufactured by Boehringer Ingelheim,Germany.Dabigatran is the first approved oral direct thrombin inhibitor in 50 years after warfarin.Dabigatran etexilate mesylate is a synthetic and low molecular weight API.The target compound is synthesized from cyano dabigatran etexilate by alcoholysis,ammonolysis and acylation.In view of the synthetic reaction route which is beneficial to industrialized production,there may exist 13 potential organic impurities in the dabigatran etexilate mesylate API,and the HPLC detection method is established,a series of detailed methodological validation experiments are carried out to verify the reliability of the method.High performance liquid chromatography and ultraviolet detector(VWD)are used to detect the related substances of dabigatran etexilate mesylate.Aglient Eclipse plus Cis column(4.6 × 150 mm,3.5 μm),the column temperature is 47 ℃,the detective wavelength is 224 nm,and the potassium dihydrogen phosphate solution of 20mmol/L mixture solution(2.7g potassium dihydrogen phosphate dissolves in 1000mL water,1mL triethylamine added,and pH adjusts to 2.5 with phosphoric acid):methanol:acetonitrile(90:5:5)is mobile phase A,methanol is mobile phase B,and gradient elution.The related substance analytical methods should have good resolution and specificity,and can effectively detect the related substances of dabigatran etexilate mesylate.Meanwhile the analytical results are accurate and reliable,and can provide technical guarantee for the quality inspection of the actual produced samples in the future.