N-NITROSAMINES IN PHARMACEUTICALS: A CURRENT PROBLEM, AN OLD REALITY

The presence of N-nitrosamines - potentially carcinogenic compounds - is being reported for more than 50 years in pharmaceutical products. However, it only gained notorious prominence in 2018, when regulatory agencies became aware of the presence of N-nitrosodimethylamine in angiotensin II receptor antagonists, drugs that are known as sartans. It did not take long for N-nitrosamine impurities to be identified in other medicines, alerting government agencies and pharmaceutical industries to evaluate and control these impurities in their products to mitigate the risk. The sources of contamination can be numerous, including the use of contaminated raw material, formation in the synthesis of active pharmaceutical ingredients or during storage, the water used in the process, and the packaging material. This review article presents the timeline of the presence of N-nitrosamines in consuming products, toxicological aspects, legislation, and analytical methods. It provides relevant information on possible sources of contamination in the production and storage process that may explain the presence of these compounds considered a cohort of concern in pharmaceuticals.