A Review of Nitrosamine Impurities Rereferred...

A Review of Nitrosamine Impurities Rereferred As Cohort of Concern Compounds in Active Drug Substance and in Finished Drug Product

Author Name : Chhote Lal Singh, Amit Singh

ABSTRACT The term nitrosamine describes a class of compounds having the chemical structure of a nitroso group bonded to any of the secondary, tertiary, or quaternary amine (R1N(-R2)-N=O[1], [2], [3] in a drug substance or excipients. Nitrosamine compounds are potent genotoxic agents in several animal species and some are classified as probable or possible human carcinogens by the International Agency for Research on Cancer [4]. They are referred to as cohort of concern compounds in the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidance for industry M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk (July 2023) [5]. USFDA [6]and EMA [7]. regulator has started investigation of Nitrosamine drug substance related impurities since 2018. Nitrosamine impurities have been found in drugs such as angiotensin II receptor blockers, histamine-2 blockers (ranitidine and nizatidine), antidiabetic medications (metformin and sitagliptin), antibiotics (rifampin and rifapentine), and smoking cessation medication (varenicline). So, the regulatory bodies is highly recommended to control of known mutagenic carcinogen like nitroso compounds, to a level below to mitigate a risk associated with exposure to the compounds.