AMPAC Analytical labs implemented test methods using LC-HRMS and GC-MS to identify trace Nitrosamines in drug substance and drug products.
Nitrosamines, such as N-Nitrosodimethylamine (NDMA), can be found at low levels in numerous items of human consumption, including cured meat, fish, beer, tobacco smoke and most recently as an impurity in various pharmaceuticals. In recent reports there have been several Angiotensin-II-receptor antagonists, AKA “Sartans”, which have been contaminated with NDMA. NDMA and Nitrosamines in general are genotoxic impurities and have been classified by the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA) as a probable human carcinogen. The EPA has determined that the maximal admissible concentration of NDMA in drinking water is 7 ng/L.
Pharmaceutical products have been on the news as these products are taken for chronic diseases; medications taken multiple times a day and in varying dosages. Regulatory agencies are actively involved in addressing the issue with detection, testing and quantitation of these impurities. New applications, renewal, synthetic route modifications and sourcing of material modifications can be subject of evaluation for the presence of Nitrosamines.
NDMA and Nitrosamines are difficult molecules to detect. General analytical tests previously used by the industry for release of API/DP may not have been able to detect the presence of Nitrosamines. AMPAC Analytical Labs has implemented methodologies to detect this class of impurities using LC-HRMS as well as GC-MS.