AMPAC analytical labs implemented test methods using LC-HRMS and GC-MS to identify trace NDMA in drug substance and drug products.
N-Nitrosodimethylamine (NDMA) is a yellow, oily liquid with a faint, characteristic odor. It is an industrial by-product or waste product of several industrial processes, such as manufacturing of unsymmetrical dimethylhydrazine (UDMH). NDMA is 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, which is highly toxic, especially to the liver, and is a known carcinogen in lab animals. The EPA classifies NDMA as a probable human carcinogen. The US Environmental Protection Agency 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 is a difficult molecule 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 NDMA. AMPAC Analytical Labs has implemented methodologies to detect this class of impurities using LC-HRMS as well as GC-MS.