Characterization of degradation products and process-related impurity of sutezolid by liquid chromatography/electrospray ionization tandem mass spectrometry

Abstract

Sutezolid was a new oxazolidinone compound used for the treatment of M. tuberculosis. This study describes the separation, characterization and in silico toxicity prediction of three degradation products and one process-related impurity of sutezolid. Sutezolid was subjected to forced degradation including hydrolytic (acidic, alkaline and neutral), oxidative, photolytic and thermal conditions according to the ICH guidelines Q1A(R2) and Q3A(R2) and yielded three degradation products. Two degradation products were formed under oxidative condition and one degradation product was formed in hydrolytic condition. This drug substance was found to be stable in thermal and photolytic conditions. The three forced degradation products were identified and characterized based on QTRAP MSⁿ, Q-TOF and NMR techniques. One process-related impurity was found in sutezolid substance and was identified and characterized by QTRAP MSⁿ and Q-TOF. The in silico toxicity prediction of the four impurities were performed using CISOC-PSCT system and CISOC-PSMT system. To the best of our knowledge, the hydrolysis product and the process-related impurity were identified for the first time.

Keywords: Degradation products; LC-MS; NMR; Process impurity; Sutezolid.