Isolation and characterisation of degradant impurities in dipyridamole formulation.

ABSTRACT

Dipyridamole is an antithrombotic drug. In the stability study of drug product of Dipyridamole, two unknown impurities (referred as DP-I and DP-II) were detected at levels of 0.25% and 0.54% by gradient reverse phase HPLC method. The drug product was subjected to stress to enhance the level of these impurities. An elegant isocratic preparative method was employed using a Reprosil CN column with a short run time of 14 min to isolate these impurities. The DP-I and DP-II were isolated with purities of 99.1% and 99.8% respectively. Structural studies of these impurities were undertaken using spectroscopic techniques such as IR, NMR and Mass. Based on the spectral data, the structures of DP-I and DP-II have been characterised to be 2,2',2″,2'″-(4-hydroxy-8-(piperidin-1-yl) pyrimido [5,4-d]pyrimidine-2,6 diyl) bis(azanetriyl) tetraethanol, 4-(2-((6-(bis (2-hydroxyethyl) amino)-4, 8-di (piperidin-1-yl) pyrimido [5,4-d] pyrimidin-2-yl) (2-hydroxyethyl) amino) ethoxy)-2, 3-dihydroxy-4-oxobutanoic acid, respectively. A detailed elucidation of the structure is presented in this article.