Nitrosamine Impurities: Assessing Concerns through Case Studies

Abstract

N-nitrosamines are potential human carcinogens that can be ingested from a range of known sources, including food, drinking water, tobacco smoke and cosmetic goods. Remarkably, their prevalence in medicinal products went undetected until mid-2018. These contaminants were first detected in the active pharmaceutical ingredient (API) of valsartan and other sartan medicines were eventually implicated. The regulatory response to the nitrosamines issue included a recommendation to all marketing authorization holders (MAHs) for human medicinal products containing chemically synthesized active pharmaceutical ingredients to evaluate the potential hazards of nitrosamines in their products and implement appropriate risk mitigation checks and balances. The objective of this review is to investigate various realms associated with investigating how these genotoxic and carcinogenic impurities may be formed during the manufacture or preservation/storage of a wide range of drugs, including sartans (losartan, valsartan), anti-diabetics (metformin, pioglitazone) and a few antacids (ranitidine) and a thorough literature review on case-studies, drug-excipient interactions, metabolic activation and other prospects.