Formation of nitrosamine impurities: Discussion and advanced method development and validation using LC-MS/MS for their detection

Nitrosamine impurities, known for their genotoxic and carcinogenic potential, have emerged as critical concerns in pharmaceutical manufacturing. Their presence in various drug substances and products has led to stringent regulatory actions globally. This report explores the formation mechanisms of nitrosamine impurities, including the subset of nitrosamine drug substance-related impurities (NDSRIs), which arise from API-specific interactions. Advanced analytical techniques such as LC-MS/MS, GC-MS/MS, and HRMS are reviewed for their efficacy in detecting and quantifying these impurities. The report also emphasizes regulatory frameworks and discusses comprehensive risk assessment strategies. By combining robust analytical methodologies and harmonized guidelines, the industry can ensure the safety and efficacy of pharmaceutical products.