Determination of Genotoxic Impurities in Pharmaceuticals
The determination of genotoxic impurities (GIs) in drug substances and pharmaceutical products is an emerging topic in pharmaceutical quality control. GIs are intermediates or reactants in the synthetic pathway of a drug substance and should be monitored at ppm (?g/g drug substance) or even ppb (ng/g) levels. This is several orders of magnitude lower than in classical impurity analysis (0.05% or 500 ppm level) or in residual solvent analysis. Analytical methods for the determination of GIs include gas chromatography (GC) and liquid chromatography (LC), both often combined with mass spectrometry (MS) detection. Some typical examples of GIs trace analysis using GC and LC are presented. The potential of on-line reaction monitoring is also discussed.