Isolation, identification and structural characterization of forced degradation products of mobocertinib using LC-MS/MS and NMR

Abstract

The main objective of this study is to develop and validate an LC-MS/MS stability-indicating method for the isolation, identification, and characterization of forced degradation products of mobocertinib under various stress conditions, utilizing LC-MS/MS and NMR techniques. Four degradation products (DP1, DP2, DP3 and DP4) were isolated. Degradation under acidic and oxidative conditions provides DP1 and DP4, respectively. Both DP2 and DP3 were obtained under basic conditions. Chromatographic development and separation were achieved using an ODS C18 column (Chemsil) with a constant flow rate of 1.0 ml/min. The mobile phase consisted of 40 % water containing 0.1 % formic acid in methanol, and detection was performed at a wavelength of 225 nm. The application of LC-MS/MS technology was utilized to separate the above degradation products. The LC-MS/MS method has validated which includes specificity, linearity, LOD and LOQ, precision, accuracy and robustness. The chemical structure of the degradation products were characterized by 1H NMR and mass spectroscopy. The above listed degradation impurities are novel and not listed in the literature. In conclusion, this study provides vital information about mobocertinib’s chemical stability and helpful in further drug development process.