Nitroso Impurities Genotoxic Impurities

N-Nitrosamines structurally characterized by a nitroso (NO) functional group covalently bonded to the nitrogen atom of an amine; Commonly, N-nitrosamines are formed by reaction of amines with a nitrosating agent under appropriate conditions (e.g., temperature, pH, concentration)

FDA has identified seven nitrosamine impurities that theoretically could be present in drug products:

• N-Nitrosodimethylamine NDMA
• N-nitrosodiethylamine (NDEA)
• N-nitroso-N-methyl-4-aminobutanoic acid(NMBA)
• N-nitrosoisopropylethyl amine (NIPEA)
• N-nitrosodiisopropylamine (NDIPA)
• N-nitrosodibutylamine (NDBA)
• and N-nitrosomethylphenylamine (NMPA)