Nitrosamine Impurities in Pharmaceutical Products: A Comprehensive Review of Sources, Analytical Detection Methods, Toxicological Risks, and Regulatory Guidelines

Nitrosamine Impurities in Pharmaceuticals: Sources, Detection, Risks, and Regulations

Abstract

Nitrosamine impurities pose a significant health risk in pharmaceutical products due to their carcinogenic, mutagenic, and DNA-damaging properties. These organic compounds can form from various sources such as raw materials, intermediates, solvents, and packaging materials used in the manufacturing and storage of active pharmaceutical ingredients (APIs) and finished drug products. Contamination has been identified in drugs like ranitidine, nizatidine, metformin, and certain angiotensin II receptor blockers (ARBs). This review provides a comprehensive overview of the chemistry, sources, formation mechanisms, and environmental influences contributing to nitrosamine formation. It also discusses key analytical techniques for detection and quantification across APIs, excipients, and packaging components. Additionally, current global regulatory frameworks from the EMA, FDA, and USP are summarized, offering insights into permissible limits and compliance strategies. The article further explores challenges and preventive measures to control nitrosamine contamination, guiding pharmaceutical industries in quality assurance and risk management practices.