Identification of forced degradation products of tedizolid phosphate by liquid chromatography/electrospray ionization tandem mass spectrometry

被引:20
作者
Lei, Yinping
Jin, Bo
Ma, Chen [1 ]
Zhang, Tingting
Li, Tong
机构
[1] Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China
关键词
Tedizolid phosphate; LC-MSn; Degradation products; NMR; In silico toxicity prediction; IN-VITRO ACTIVITY; GRAM-POSITIVE PATHOGENS; CISOC-PSCT; OXAZOLIDINONE; TR-701; INFECTIONS; PREDICTION; TOXICITY; STRAINS;
D O I
10.1016/j.jpba.2017.03.006
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
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 MSn 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 MSn 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. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:221 / 231
页数:11
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