A Review on Analysis of Genotoxic Impurities

Abstract: Genotoxic impurity can be defined as a chemical or other agent that damages cellular DNA, resulting in mutations or cancer. Genotoxic impurities impact the genetic material by means of mutations through chromosomal breaks, rearrangements, covalent binding or insertion into the DNA during replication. These changes in the genetic material, caused by the exposure to very low levels of a genotoxic chemical, can lead to cancer. Determination of 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, requires highly sensitive analytical methodologies, which poses tremendous challenges on analytical communities in pharmaceutical R & D. Therefore, sensitive and sophisticated analytical methodologies are deemed necessary in order to be able to test and control genotoxic impurities in drug substances. Thus, it is very important to identify genotoxic impurities in drugs followed by monitoring and control at very low levels to ensure safety to the public. This review demonstrates guidelines the various regulatory guidelines to control the genotoxic impurities in drug substances and the analytical approaches reported in the literature for the analysis of the hazardous genotoxic impurities and the strategies used to enhance the sensitivity and the separation techniques for the analysis of such impurities.

Keywords: Genotoxic impurities GIs, Regulatory guidelines, ICH, EMEA, Threshold, Analytical approach

Edition: Volume 9 Issue 8, August 2020,

Pages: 1017 - 1027