Title: 'A to Z' of drug substances and its nitrosamine impurities with the control strategy in the pharmaceuticals

Authors: Balaji Nagarajan

Addresses: Principal Scientist, Apicore LLC, New Jersey, 08520, USA

Abstract: xNitrosamines pose a significant safety concern for the pharmaceutical industry due to their suspected carcinogenic and mutagenic properties. This reviews nitrosamine impurities in pharmaceutical products, focusing on formation mechanisms, detection methods, and control strategies. It outlines nitrosamine sources from manufacturing processes and interactions with nitrosating agents. Various nitrosamines, such as NDMA, NDEA, and NMPA, are discussed alongside susceptible drug classes, including angiotensin II receptor blockers, H2 receptor antagonists, antidiabetic agents, and antimicrobial drugs. The review covers analytical detection methods, challenges, and regulatory requirements from entities like the EMA and USFDA. Control strategies involving good manufacturing practices and supplier audits are emphasised to reduce nitrosamine levels. The review also includes case studies on sartan drugs and relevant solvents as practical applications of managing nitrosamine contamination. Conclusively, it outlines future directions for effectively mitigating nitrosamine impurities to maintain pharmaceutical safety and integrity.

Keywords: nitrosamine impurities; control strategy; pharmaceutical safety; drug substances; regulatory frameworks; GMP; good manufacturing practices; ARBs; angiotensin II receptor blockers.

DOI: 10.1504/IJNBM.2026.153240

International Journal of Nano and Biomaterials, 2026 Vol.11 No.3, pp.279 - 305

Received: 21 Apr 2025
Accepted: 09 Dec 2025
Published online: 29 Apr 2026 *

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