High Resolution Liquid Chromatography-Mass Spectrometry Combined with Forced Degradation and Nuclear Magnetic Resonance for Analysis of Novel Impurity in Torasemide Injection and Evaluation of Impact of Residual Oxygen Levels on Its Formation
10.19756/j.issn.0253-3820.241444
- VernacularTitle:液相色谱-质谱联用结合强降解及核磁共振分析托拉塞米注射液新杂质及残氧量水平的影响
- Author:
Hai-Wei YE
1
;
Li-Ping ZHOU
;
Min LI
;
Jin-Sheng LIN
Author Information
1. 台州职业技术学院化学制药研究所,台州 318000
- Keywords:
High performance liquid chromatography-ion trap time-of-flight mass spectrometry;
Forced degradation;
Torsemide sulfonamide methylene cyclic compound;
Impurity research;
Formaldehyde
- From:
Chinese Journal of Analytical Chemistry
2025;53(10):1732-1740,中插54-中插57
- CountryChina
- Language:Chinese
-
Abstract:
Drug impurity control is essential for ensuring pharmaceutical quality.In this study,an unknown impurity at relative retention time(RRT)of 0.45 in Torasemide injection was systematically investigated using high performance liquid chromatography-ion trap time-of-flight mass spectrometry(LC-IT-TOF-MS/MS),forced degradation studies,and nuclear magnetic resonance(NMR)spectroscopy,aiming to elucidate its chemical structure,propose a formation mechanism,and establish a control strategy.By analysis of the ultraviolet absorption spectrum and high-resolution MS1 and MS2 data of the impurity,its possible structure was postulated.Subsequently,the target impurity was prepared via forced degradation experiment,and its structure was confirmed by NMR spectroscopy.A detailed analysis of its formation mechanism revealed that Torasemide first hydrolyzed in solution to form Torasemide sulfonamide,and then underwent condensation,dehydration,and cyclization reactions with trace amounts of formaldehyde in the excipient polyethylene glycol(PEG)400 to generate the impurity.It was experimentally proven that the target impurity was related to the residual oxygen content in Torasemide injection.Ultimately,by optimizing the prescription process,the target impurity level was controlled below the individual impurity limit of the final product(≤0.3%).This study provided valuable insights for enhancing the quality control of Torasemide injection.
