Identification of Tartaric Acid Adduct Impurities in Dipyridamole Capsule Formulation Related Substances Method

Abstract

Two tartaric acid adduct degradation products namely dipyridamole tartaric acid monoester and dipyridamole ditartaric acid ester are observed in a dipyridamole capsule formulation. The adduct impurities are inevitable in the formulation due to the interaction of multi-layers of dipyridamole on tartaric acid pellets. Present study reported a simple procedure for generating these two major adducts degradation products from a mixture of dipyridamole drug substance and tartaric acid by stress study. The obtained stress mixture was characterized by liquid chromatography-tandem mass spectrometry (LC-MS) to assure the identity of adduct degradant impurities. The obtained solid stress mixture was stable for more than one year and the prepared solution can be used as reference solution to identify both the degradants during related substance analysis. Practically, the identification of tartaric acid degradants applied to the British pharmacopeia monograph related substances method, where no mechanism for identification of these adduct impurities was described. This study establishes relative retention times for the British pharmacopeia method, which enables the chemist to monitor these two major degradants during quality control release testing and shelf life stability. The same kind of experimental approach for identifying tartaric acid adduct impurities in the British pharmacopeia method can be extended to any of the in-house laboratory-developed related substance methods.