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International Journal of Zoology and Applied Biosciences Research Article
Nitrosamines: Emerging chemical contaminants of concern in pharmaceutical and biological systems
Anusha G, Hemanth A, Lalitha Srilekha R, Alekhya G, Niharika G, Likhita A and Sai Poojitha M
Year : 2025 | Pages: 364-369
Received on: 10/09/2025
Revised on: 22/10/2025
Accepted on: 14/11/2025
Published on: 30/11/2025
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Anusha G, Hemanth A, Lalitha Srilekha R, Alekhya G, Niharika G, Likhita A and Sai Poojitha M( 2025).
Nitrosamines: Emerging chemical contaminants of concern in pharmaceutical and biological systems
. International Journal of Zoology and Applied Biosciences, 10( 6), 364-369.
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Abstract
Nitrosamines are a class of compounds characterized by a nitroso group bonded to an amine (R?N(-R?)-N=O) and are commonly found in water, food, and pharmaceutical products. Their presence in drug substances has raised significant global concern due to their genotoxic and carcinogenic potential. Nitrosamines can form through nitrosation reactions between amines (secondary, tertiary, or quaternary) and nitrous acid, often derived from nitrite salts under acidic conditions. Regulatory agencies such as the FDA, EMA, and WHO have undertaken comprehensive investigations to identify, control, and mitigate nitrosamine impurities in active pharmaceutical ingredients (APIs) and finished products. These impurities are classified as small-molecule nitrosamines (e.g., NDMA, NDEA, NMBA) and nitrosamine drug substance-related impurities (NDSRIs), which are structurally related to APIs. Root causes include the presence of amines in raw materials, cross-contamination from recovered solvents, inadequate process control, and nitrite-containing excipients. Even potable water and packaging components can contribute to contamination. To address these risks, the FDA recommends a three-step mitigation strategy: risk assessment of APIs and products, confirmatory testing of identified impurities, and regulatory submission of implemented control measures. Acceptable intake limits have been defined across major health authorities to minimize carcinogenic risk. The International Council for Harmonisation (ICH M7[R2]) also categorizes nitrosamines as “cohort of concern” compounds, requiring control at negligible risk levels. Comprehensive understanding of nitrosamine formation pathways, stringent process optimization, and supplier quality oversight are therefore essential to ensure pharmaceutical safety and regulatory compliance.
Keywords
Nitrosamines, Genotoxic impurities, NDSRI, FDA, ICH M7(R2), Pharmaceutical contamination.
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© The Author(s) 2025. This article is published by International Journal of Zoology and Applied Biosciences under the terms of the Creative Commons Attribution 4.0 International License (creativecommons.org), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
