Nitrosamines & Nitrites in Pharmaceuticals: From Regulatory Updates to Analytical Solutions

The control of nitrosamines and nitrites in pharmaceuticals remains a critical challenge for MAHs, API manufacturers, and regulatory bodies worldwide. Recent updates from EMA and FDA guidance have expanded the scope from small nitrosamines to nitrosamine drug substance-related impurities (NDSRIs), imposing stricter requirements for risk assessments, confirmatory testing, and dossier compliance. Analytical complexities arise from trace-level detection, artefact formation, and matrix interferences, demanding advanced mass spectrometry and robust method validation. Nitrites, ubiquitous in excipients and raw materials, represent a key root cause of in situ nitrosamine formation and require systematic monitoring. This presentation will explore state-of-the-art analytical approaches, including LC-MS/MS, HRMS, ion chromatography, and NAP test applications, alongside case studies on sensitivity, specificity, and robustness.