Isolation and characterization of related substances in alogliptin benzoate by LC-QTOF mass spectrometric techniques.
A highly specific and efficient LC-QTOF mass spectrometric method was developed for the separation and characterization of process related substances and the major degradation products in alogliptin benzoate and its tablets. The separation was performed on Phenomenex Gemini-NX C18 column (250mm×4.6mm, 5μm) using 0.2% formic acid-0.2% ammonium acetate in water as mobile phase A, acetonitrile and methanol (60:40, v/v) as mobile phase B in linear gradient elution mode. Forced degradation studies were also conducted under ICH prescribed stress conditions. Alogliptin benzoate and its tablets were tending to degrade under acid, alkaline, oxidative and thermal stresses, while relatively stable to photolytic stress. A total of seven related substances were detected and characterized through liquid chromatography-high resolution QTOF mass spectrometry techniques, including process related substances and degradation products, and two of them were further synthesized and characterized by NMR spectroscopy. Based on the related substances elucidation and the plausible formation mechanisms, efficient approaches were proposed to reduce or eliminate related substances, and in consequence the quality of alogliptin benzoate and its tablets have been promoted obviously. Therefore, the impurity profiles obtained are critical to the quality control and manufacturing processes optimization and monitoring of alogliptin benzoate and its tablets.
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Yuting
Y
Lu
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Danyi
D
Yang
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
Zhiyu
Z
Li
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China. Electronic address: hangtj@cpu.edu.cn.
Taijun
T
Hang
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cqsongmin@sina.com.
Min
M
Song
D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D004355:Drug Stability; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000032:analysis*; D007202:Indicators and Reagents; D057230:Limit of Detection; D010084:Oxidation-Reduction; D010782:Photolysis; D010880:Piperidines / Q000032:analysis*; D015203:Reproducibility of Results; D013607:Tablets; D053719:Tandem Mass Spectrometry; D014498:Uracil / Q000031:analogs & derivatives* / Q000032:analysis
D007004:Hypoglycemic Agents; D007202:Indicators and Reagents; D010880:Piperidines; D013607:Tablets; D014498:Uracil; C520853:alogliptin
Alogliptin benzoate; LC-QTOF mass spectrometry; Related substances