Identification and characterization of the degradation products of prasugrel hydrochloride tablets using LC-MS technique

ABSTRACT

New high-performance liquid chromatography method was developed for the determination of prasugrel HCl-related substances. Impurity profile of prasugrel HCl was established by studying the degradation profile of it as an active pharmaceutical ingredient, for the first time, in the tablet form. Two significant unknown degradation products (impurities) were detected and characterized, to the best of our knowledge; these impurities have not been previously reported in the literature. The first one resulted from acidic, basic, and neutral hydrolyses of prasugrel; it was nominated as impurity 1 (5-(2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2(3H)-one), its structure was proposed using liquid chromatography/mass spectrometry technique. The second degradant was nominated as impurity 2 (5-(2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-7a-hydroxy-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one) that formed upon neutral hydrolysis of prasugrel with magnesium stearate; this impurity was identified using nuclear magnetic resonance and LC-MS techniques. Based on these findings, other lubricant materials should be used in prasugrel tablets instead of magnesium stearate to avoid formation of such impurity. Prasugrel HCl was susceptible to hydrolytic and oxidative degradation, whereas it was stable under these conditions.

GRAPHICAL ABSTRACT

KEYWORDS:

• Degradation products
• DEPT-NMR
• impurity profile
• LC-MS
• magnesium stearate
• prasugrel tablets

Acknowledgments

The authors gratefully acknowledge the financial supports from Tabuk Pharmaceuticals Company and the University of Jordan, Deanship of Scientific Research.