A Review on N-nitrosamine Impurity

Abstract: Nitrosamines are a category of substances that have a nitroso group linked to an amino group in their molecular structure. They are a category of carcinogens developed as a by-product of drug synthesis and also constituted in the presence of sodium nitrite or nitric acid and secondary amines (like dimethyl amines and diethyl amine) that must be monitored in drug production. In mid-June 2018, the Food and Drug Administration and the European Medicines Agency became aware of the existence of an impurity called N-nitrosamine in some frequently used medications, such as those for blood pressure, antacids, and diabetes. N-nitrosamines are of major concern because the ICH M7 (R1)2 guideline categorizes them as Class 1 impurities or mutagenic carcinogens, and the International Agency for Cancer Research categorizes them as potential carcinogens. The existence of N-nitrosamines in pharmaceutical drugs must be minimized to the greatest extent possible and must be at or below the threshold based on ICH M7(R1)2 fundamentals for materials in the "cohort of concern" described in this guideline and measured based on lifetime constant exposure.