Application note: Rapid Analysis of Genotoxic Nitrosamines by HPLC-MS/MS

Genotoxic impurities (GTI’s) are intermediate, reactive products or degradants formed during drug synthesis, formulation or storage.

These impurities can damage human genetic material at very low levels, leading to DNA mutations which can contribute to tumorigenesis and carcinogenicity. Because of these compounds’ potencies, they pose a threat to the safety of medication. To prevent large-scale recall incidents, such as those involving nelfinavir mesylate (Viracept) in 2007, or valsartan (Diovan) in 2018, regulatory agencies including the US FDA and the European Medicines Agency (EMA), have issued guidelines on the allowable limits of genotoxic impurities in pharmaceutical products to ensure their safety. These guidelines state exposure to GTI’s must be below the threshold of toxicological concern (TTC) of 1.5 µg per day.