Lei Yinping, Jin Bo, Ma Chen, Zhang Tingting, Li Tong
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. 2017 May 30;139:221-231. doi: 10.1016/j.jpba.2017.03.006. Epub 2017 Mar 7.
In this study, stress degradation behavior of tedizolid phosphate was investigated and structural characterization of its degradation products were performed with the use of the UPLC-MS and LC-HRMS. The toxicity prediction of the degradation products was performed with web-based prediction system. Tedizolid phosphate was subjected to forced degradation under hydrolytic (acid, base and neutral), oxidative, photolytic and thermal conditions in accordance with ICH guidelines Q1A(R2). The drug was degraded significantly under acid, base and oxidative conditions, while it was relatively stable to neutral, thermal and photolytic conditions. A total of four degradation products were formed. All of them have been identified and characterized based on QTRAP MS and accurate mass measurements. To the best of our knowledge, three of these impurities were identified for the first time and two of them further synthesized and characterized by NMR spectroscopy.
在本研究中，对替加环素磷酸酯的应力降解行为进行了研究，并使用超高效液相色谱-质谱联用仪（UPLC-MS）和液相色谱-高分辨质谱仪（LC-HRMS）对其降解产物进行了结构表征。利用基于网络的预测系统对降解产物进行了毒性预测。按照国际人用药品注册技术协调会（ICH）指南Q1A(R2)，使替加环素磷酸酯在水解（酸、碱和中性）、氧化、光解和热条件下进行强制降解。该药物在酸、碱和氧化条件下显著降解，而在中性、热和光解条件下相对稳定。共形成了四种降解产物。所有降解产物均已基于QTRAP质谱和精确质量测量进行了鉴定和表征。据我们所知，其中三种杂质为首次鉴定，其中两种还通过核磁共振光谱进一步合成和表征。
