Čes. slov. farm. 2024, 73(4):228-232 | DOI: 10.36290/csf.2024.041

Contamination of drugs with nitrosamines, a restored problem

Martin Doležal, Petr Kastner

Katedra farmaceutické chemie a farmaceutické analýzy, Farmaceutická fakulta UK v Hradci Králové

This review article deals with the issue of nitrosamines as impurities in pharmaceuticals. Medicinal products contaminated with nitrosamine raise legitimate concerns about the safety of medicinal use. Nitrosamines are known to be carcinogens and mutagens. This applies not only to valsartan and all tetrazole-containing angiotensin II receptor blockers, but also to ranitidine, nizatidine, pioglitazone, metformin, rifampicin, rifabutin, varenicline and other drugs, some of which have already been withdrawn from clinical practice. The detection of impurities above the limit in pharmaceutical substances then leads to interruptions in production and shortages of some drugs in practice. If the relevant amine reacts under appropriate conditions with a nitrosating agent, impurities of the nitrosamine type can be formed at practically any stage of the synthesis of the pharmaceutical substance and also throughout the lifetime of the finished medicinal product. Drug regulatory bodies around the world have set strict nitrosamine contamination guidelines for all medicinal products.

Keywords: nitrosamines, production of active pharmaceutical substances, contaminants.

Accepted: December 9, 2024; Published: January 1, 2025  Show citation