Emerging Concerns of Nitrosamine Impurities in Drug Perspectives
DOI:
https://doi.org/10.5530/ajphs.2025.15.85Keywords:
Nitrosamine, N-nitrosodimethylamine, Carcinogens, FDAAbstract
Nitrosamine impurities have emerged as a global pharmaceutical concern since the detection of N-nitrosodimethylamine (NDMA) in valsartan in 2018. Recognised as probable human carcinogens, nitrosamines have since been identified in several essential drugs, including ranitidine, metformin, and ARBs (Angiotensin II Receptor Blockers), prompting large-scale recalls, regulatory investigations, and significant industry impact. Their presence is primarily linked to synthesis pathways, contaminated raw materials, degradation processes, and interactions with packaging. This review discusses the chemical nature of nitrosamines, their formation mechanisms, case studies, analytical methods for detection, and current regulatory frameworks from the FDA, EMA, and ICH. Risk assessment strategies, industry responses, and future perspectives for robust impurity management are also explored.
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