Nitrosamine Impurities
History of Nitrosamine Impurities In July 2018, USFDA has alerted healthcare professionals to withdraw the drug, valsartan, from the market due to the presence of an impurity, N-nitrosodimethylamine (NDMA). This impurity is highly toxic and is considered as a "probable human carcinogen" meaning it can cause cancer. Nitrosamines are classified by the ICH M7(R1) Guideline as Class 1 impurities, “ known mutagenic carcinogens ,” based on both rodent carcinogenicity and mutagenicity data Other Nitrosamine Impurities The investigation of NDMA in valsartan leads to the detection of some more nitrosamine impurities in drugs viz., N-nitrosodiethylamine (NDEA), N -nitrosodiisopropylamine (NDIPA), N – nitrosoethylisopropylamine (NEIPA), N -nitroso-N-methyl-4-aminobutyric acid (NMBA) etc. Mechanism of Formation Nitrosamines are formed when nitrites, which can be formed from nitrates, react with a secondary or tertiary amine to p...