The synthesis of drug substances involves the use of reactive chemicals, reagents, solvents, catalysts, and other processing aids. As a result of chemical synthesis or subsequent degradation, impurities resides in the drug substances and associated drug products.

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Nitrosamines impurities belong to a family of carcinogens impurities that are formed by the nitrosating reaction between secondary, tertiary and Quaternary amines and nitrous acid (nitrite salt under acidic conditions).

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Nitrosamines have been classified by the ICH M7(R1) Guideline as Class 1 impurities, “known mutagenic carcinogens,” on the basis of rodent carcinogenicity and mutagenicity data. Due to known carcinogenicity of Nitrosamine impurities, various regulatory agencies provide guidance for drug substance and drug product manufacturer to perform risk assessment to quantify and control Nitrosamine impurities below Specification limit.

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N-Nitrosodimethylamine (NDMA), N-Nitrosodiethylamine (NDEA), N-Nitroso-N-methyl-4- aminobutyric acid (NMBA), N-Nitrosomethylphenylamine (NMPA), N-Nitrosoisopropylethylamine (NIPEA), N-Nitrosodiisopropylamine (NDIPA), 1-methyl-4-nitrosopiperazine (MeNP), NDimethylamine (NDBA) etc. are common Nitrosamine impurities found in drug substance and drug Product. Along with common Nitrosamine impurities, now a days Drug Substance-related Nitrosamine Impurities (NDSRIs) identified in drug substance and drug product like drug Duloxetine, Melatonin, Metalazone, Clonidine etc.

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Due to common nitrosamines’ physiochemical properties (low molecular weights, some volatility and high toxicity), the analytical methods for nitrosamines need to have specificity, excellent chromatographic separation, and highly sensitive detection capability.

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In recent years, RRC approached Premier Analytical Services to develop a standard screening method determination of Nitrosamines from pharmaceutical products. RRC is well equipped with all the required equipment to perform analytical test including, LCMSMS which is high sensitive and selective to quantify Nitrosamine impurities in drug substance and drug product.

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