Forced degradation studies of perampanel: Identification and characterization of degradation products by Q-Orbitrap and NMR

Perampanel (PER) is a first-in-class anti-epileptic drug, non-competitive negative allosteric AMPA receptor antagonist1. Objective of this work is identified and characterize PER degradation products (DP) and developing a CLAE-DAD methodology. PER was exposed to acidic and basic hydrolysis, metal ions, oxidation and photodegradation2, 3. PER tablets with acid, basic and oxidative excipients were stored at room temperature and accelerated stability chamber for 24 months. All samples were analyzed by HPLC-DAD. The identification and characterization of the PDs were performed by HRMS Q-Orbitrap and 1H and 13C NMR. DP-1 and DP-2 were formed in acid hydrolysis and in acid tablets stored in accelerated stability chamber. DP-3 was formed in oxidative condition. In alkaline hydrolysis, three unidentified products were formed. To conclude, it is necessary to identify the PDs of the basic condition and validate the analytical method indicative of stability.