Nitrosamine & Mutagenic Impurities Application Guide

Mutagenic impurities in APIs and drug products pose a significant risk to health and safety—even in small quantities—and thus are a major concern for drug makers. Mutagenic impurities can damage DNA, leading to mutations and potentially cancer. Nitrosamines are formed by chemical reactions that occur during API manufacturing whether from starting materials, intermediates, reactants, reuse of solvents and by-products; they can form through degradation products generated during formulation or storage or from environmental contaminants. Recently, nitrosamines have been found in sartan drugs, a class of medications used to treat high blood pressure and heart failure, prompting recalls of angiotensin receptor blockers (ARBs)—valsartan, losartan, and irbesartan—which were contaminated with N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA), two carcinogenic impurities. Since then, several other N-nitrosamines have also been identified and are being investigated by regulators: N-Nitrosodiispropylamine (NDIPA), N-Nitrosoethylisopropylamine (NEIPA), N-Nitrosodibutylamine (NDBA), and N-Nitroso-N-methyl-4-aminobutyric acid (NMBA). Nitrosamines have now also been identified in ranitidine medications (which are used to treat heartburn and acid reflux) and metformin, an oral diabetes medication. Za odpiranje dokumenta
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