Identification, isolation, characterization, and UHPLC quantification of potential genotoxic impurities in linagliptin

Journal of Separation Science
Yiwen HuangChunyan Min

Abstract

During the stress testing of linagliptin, one unknown degradation product (impurity I) on acidic conditions was detected by using high-performance liquid chromatography and subsequently isolated, identified, and characterized by the spectral data (MS, MS/MS, 1D and 2D NMR spectroscopy, and IR spectroscopy) and finally subjected for mechanism analysis. The degradation product (impurity I) and another process-related impurity (impurity II) of linagliptin were found to contain the structural alerts of N-acylated aminoaryl and alkyl halide, respectively, which were both potential genotoxic substances. Hence, a rapid and facile ultra high performance liquid chromatography method was developed for the simultaneous determination of these two potential genotoxic impurities at ppm levels in linagliptin. The factors involved in the method development were discussed and this method was fully validated as per International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines, which proved the method sensitive, selective, and robust. The presented method has been successfully applied to the analysis of real samples from multiple batches. This study will help to risk management of...Continue Reading

References

Dec 8, 2009·International Journal of Toxicology·Joel P BercuTimothy J McGovern
Jan 5, 2011·Journal of Pharmaceutical and Biomedical Analysis·N V V S S RamanK Ratnakar Reddy
Jun 30, 2016·Journal of Chromatographic Science·Abeer Hanafy, Hoda Mahgoub
Aug 16, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yiwen HuangFuli Zhang

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Citations

Apr 5, 2019·Journal of Analytical Methods in Chemistry·Raquel Balestri Heleno FerreiraClésio Soldateli Paim
Apr 7, 2021·Journal of Chromatographic Science·Sunitha GurralaPanikumar Durga Anumolu
Nov 9, 2018·Analytical Chemistry·Valentina D'AtriDavy Guillarme

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