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- Title
HPLC-MS Analysis of Four Potential Genotoxic Impurities in Alogliptin Pharmaceutical Materials.
- Authors
Al-Sabti, Bashar; Harbali, Jehad
- Abstract
Background: Pyridine, 3-aminopyridine, 4-dimethylaminopyridine, and N, N-dimethylamine are reactive bases that may be used in the preparation of the pharmaceutical ingredient alogliptin (ALO). They are considered as potentially genotoxic impurities (PGIs) since they contain electrophilic functional groups. Therefore, they should be monitored at the allowed limits in ALO. Objective: The aim of this study was to develop a novel liquid chromatography-mass spectrometry (LC-MS) method to estimate quantities of pyridine, 3-aminopyridine, 4-dimethylaminopyridine, and N, N-dimethylaniline impurities in ALO drug material. Methods: The separation was performed on Kromasil CN (250mm-3.9mm, 3.5 mm) column in reversed phase mode. The mobile phase was amixture of water-methanol (55:45, v/v) containing 2.5mM ammonium acetate and 0.1% formic acid. Impurities were detected by MS in selected ionmonitoringmode at m/z 80, 95, 122, and 123 for pyridine, 3-aminopyridine, N, N-dimethylaniline, and 4-dimethylaminopyridine, respectively. The flow rate of the method was 0.5mL/min. Results: The sensitivity of the method was excellent at levels much less than the allowed limits. The method had excellent linearity in the concentration ranges of Quantitation Limit (QL)-150% of allowed limits and coefficients of determination were above 0.9990. The recovery ratios were in the range of 93.56-110.28%. Conclusion: Results showed good linearity, precision, accuracy, sensitivity, selectivity, robustness, and solution stability. The studied method was applied to test two samples of raw materials and one sample of tablets. Highlights: The method discussed here could be very useful for controlling potentially genotoxic impurities (PGIs) levels in ALO during its synthesis, and for QC testing of ALO raw materials before using them in the preparation of pharmaceutical products.
- Subjects
LIQUID chromatography-mass spectrometry; FORMIC acid; RAW materials; DRUGS
- Publication
Journal of AOAC International, 2022, Vol 105, Issue 2, p362
- ISSN
1060-3271
- Publication type
Article
- DOI
10.1093/jaoacint/qsab152