Application of Quantitative NMR (qHNMR) towards Establishment of Pharmaceutical Reference Standard; A Case of a Ticagrelor Process Impurity.

Quantitative proton NMR (qHNMR) methodology was employed for the stoichiometric (free base and the corresponding counterion) assessment of a ticagrelor process impurity, also referred to in the United States Pharmacopeia (USP), Pharmacopeial Forum as Ticagrelor Related Compound A (RC A), [(1R,2S)-2-(3,4-difluorophenyl)cyclopropan-1-amine (R)-mandelate], also called as Tica amine mandelate, a critical impurity that, when present during manufacturing, has a limit of not more than 0.0008%. The Tica amine is also a listed impurity E in the Ticagrelor monograph, in European Pharmacopeia.