Format

Send to

Choose Destination
J Pharm Biomed Anal. 2016 Sep 5;128:253-263. doi: 10.1016/j.jpba.2016.04.032. Epub 2016 May 6.

Isolation and characterization of related substances in alogliptin benzoate by LC-QTOF mass spectrometric techniques.

Author information

1
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
2
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
3
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China. Electronic address: hangtj@cpu.edu.cn.
4
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cqsongmin@sina.com.

Abstract

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.

KEYWORDS:

Alogliptin benzoate; LC-QTOF mass spectrometry; Related substances

PMID:
27281581
DOI:
10.1016/j.jpba.2016.04.032
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center