title: Identification of forced degradation products of tedizolid phosphate by liquid chromatography/electrospray ionization tandem mass spectrometry.
abstract: 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-MSnand 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 MSnand 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.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors.forename: Yinping
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China. Electronic address: mach@imm.ac.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Ma
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D006868:Hydrolysis; D010755:Organophosphates / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism*; D010080:Oxazoles / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D010755:Organophosphates; D010080:Oxazoles; C515040:tedizolid phosphate
keywords: Degradation products; In silico toxicity prediction; LC–MS(n); NMR; Tedizolid phosphate