Detection Techniques for Eliminating Pharmaceutical Impurities: Focus on Genotoxic Impurities

The elimination of organic impurities to produce highly pure drug substances is an important goal of process chemistry. For the detection of general impurities, hyphenated techniques(such as HPLC,Electrophoresis) play a critical role in rapid structural identification (qualitative detection) and in understanding the mechanisms of formation of the impurities, enabling informed decisions to control and eliminate the impurities resulting from the chemical process where possible. Drug impurity profiling, i.e. identification, structure elucidation and quantitative determination of impurities and degradation products in bulk drug materials and pharmaceutical formulations is one of the most important fields of activities in modern pharmaceutical analysis. The reason for the increased importance of this area is that unidentified, potentially toxic impurities are health hazards and in order to increase the safety of drug therapy, impurities should be identified and determined by selective methods. Genotoxic impurities (GTIs) in pharmaceuticals at trace levels are of increasing concerns to both pharmaceutical industries and regulatory agencies due to their potentials for human carcinogenesis. Determination of these impurities at ppm levels requires highly sensitive analytical methodologies, which poses tremendous challenges on analytical communities in pharmaceutical R&D. This article provides an industrial perspective with regard to the analysis of various structural classes of GTIs that are commonly encountered during chemical development. The primary aim of this review is to highlight recent advances in qualitative and quantitative detection of impurities at trace levels, with a particular focus on GTIs.