UPLC-Q-TOF-MS/MS and NMR studies for the structural characterization of degradation impurities of rimegepant

Rimegepant is a type of medication classified as a calcitonin gene-related peptide (CGRP) receptor antagonist, used to treat migraines. The present research focused to identify and characterize its degradation products using the liquid chromatography-high-resolution mass spectrometry (Q-TOF-HRMS) and nuclear magnetic resonance spectroscopy (NMR). The degradation profile of rimegepant was evaluated using forced degradation studies, which included exposure to hydrolysis, oxidation, photolysis, and thermal conditions. The drug degraded under hydrolytic and oxidative conditions whereas it was found to be stable under photolytic and thermal conditions. An Acquity CSH C18 column (2.1 × 100 mm; 1.7 µm) was used to separate the analytes using a mobile phase of 0.1% formic acid in water and 0.1% formic acid in acetonitrile eluting in gradient mode at a flow rate of 0.3 mL/min. The degradation products were separated and identified using the mass fragmentation and accurate mass information obtained from LC-MS. A preparative HPLC was used to isolate the major degradation products for structural identification through 1D and 2D NMR studies. According to ICH Q2 (R1) guidelines, the developed UHPLC-PDA method was validated for its accuracy, precision, linearity, and specificity.