V. Mutha, B. Katari, Muralidharan Kaliyaperumal
May 4, 2018
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Journal
Analytical Chemistry Letters
Abstract
Abstract Dabigatran etexilate mesylate is a prodrug salt prescribed to prevent stroke with atrial fibrillation. It was subjected to stability testing by hydrolysis in both acid and basic media at room temperature. The degradation resulted in two degradants in each medium and one of which was found to be common in both the media. The degradants have been isolated by mass based preparative HPLC and SFC. All of them were unambiguously characterized by HRMS and extensive NMR (including 2D) spectroscopic techniques. Of the three impurities isolated (referred as DP-1, 2 and 3), DP-2 and DP-3 are being reported for the first time. DP-1 was identified earlier but was not characterized by NMR. DP-3 was obtained in both acid and base mediated hydrolysis. Based on 1D-NMR, 2D-NMR and HRMS spectral data, the structures of degradation products were confirmed as (Z)-3-(2-((4-(N’-(hexyloxycarbonyl) carbamimidoyl) phenylamino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido) propanoicacid for DP-1 (Known); 2-((4-carbamimidoylphenyl amino)methyl)-1-methyl-1H-benzo[d]imidazole-5-carboxylic acid for DP-2 (New); (Z)-2-((4-(N’-(hexyloxycarbonyl) carbamimidoyl) phenylamino)methyl)-1-methyl-1H-benzo[d]imidazole-5-carboxylic acid for DP-3 (New).