Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
J Pharm Biomed Anal. 2019 May 30;169:196-207. doi: 10.1016/j.jpba.2019.03.005. Epub 2019 Mar 6.
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 MS, Q-TOF and NMR techniques. One process-related impurity was found in sutezolid substance and was identified and characterized by QTRAP MS 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.
舒他西林是一种新型噁唑烷酮类化合物，用于治疗结核分枝杆菌。本研究描述了三种降解产物和一种工艺相关杂质的分离、表征和计算机毒性预测。根据 ICH 指南 Q1A(R2)和 Q3A(R2)，舒他西林进行了强制降解，包括水解（酸性、碱性和中性）、氧化、光解和热条件，产生了三种降解产物。两种降解产物在氧化条件下形成，一种降解产物在水解条件下形成。该药物在热和光解条件下稳定。基于 QTRAP MS、Q-TOF 和 NMR 技术，对三种强制降解产物进行了鉴定和表征。在舒他西林物质中发现了一种工艺相关杂质，并通过 QTRAP MS 和 Q-TOF 进行了鉴定和表征。使用 CISOC-PSCT 系统和 CISOC-PSMT 系统对这四种杂质进行了计算机毒性预测。据我们所知，首次鉴定出了水解产物和工艺相关杂质。
