A Study of Nitrosamine Impurities and Regulations Governing their Presence in Drug Products

The seriousness of presence of nitrosamines came to Limelight after USFDA and EMEA declared in July 2018 that N-Nitroso dimethylamine and N-N-NDMA are focused on the pharmaceutical medicinal products and particularly used in case of SARTANS that are used in the treatment of Hypertension and Angiotensin II receptor blockers. Later the list was expanded to include Histamine-2 blocker Ranitidine and Diabetes drug Pioglitazone. Reaction of Urea Derivatives, Secondary amide carbamates and amines with Nitrogenous agent and nitrates lead to formation of Nitrosamines. The Oxidation state of nitrogen is +3. The Reasons for Presence of Nitrosamines in Pharmaceutical Products can be due to Product Degradation, Catalysts, solvents, Chemical reagents, Cross Contamination, Manufacturing Process and Contamination of Raw Materials. Technologies like Gas Chromatography, Mass Spectroscopy, Light Chromatography Mass spectroscopy are used to detect Nitrosamine Contamination. N-Nitrosamines categorized as “Cohort of concern” in ICH guidelines due to their potential mutagenic and carcinogenic nature. N-Nitroso dimethylamine and N-Nitroso diethylamine are classified as Class 2A human carcinogens by IARC-International Agency for Research and Cancer. This study focused on profile of nitrosamine impurities and regulations governing their presence in drug products.