Recent advances in analysis of hazardous genotoxic impurities in pharmaceuticals by HPLC, GC, and CE

Abstract

ABSTRACTNowadays, genotoxic impurities in pharmaceuticals at lower levels are of increasing concerns not only to pharmaceutical industries but also for the regulatory agencies due to their risks for human carcinogenesis and, thus, requiring manufacturers to pay extra attention for their analysis and control. The need to determine these impurities at trace levels, based on the threshold of toxicological and daily dose, taking into consideration the often reactive and labile nature of genotoxic impurities, which poses significant analytical challenges. Therefore, sensitive and sophisticated analytical methodologies are deemed necessary in order to be able to test and control genotoxic impurities in drug substances. This review demonstrates the approaches reported in the literature for the analysis of the hazardous genotoxic impurities and the strategies used to enhance the sensitivity such as using ion spray-mass spectrometry and the separation techniques for the analysis of such impurities.