Hunt for NDSRIs: Unveiling Hidden Threats with the Novel 15 N-Enriched NAP Test
Abstract
High Resolution Image Download MS PowerPoint Slide Nitrosamine impurities, particularly nitrosamine drug substance-related impurities (NDSRIs), have emerged as a critical concern in pharmaceutical manufacturing due to their potential carcinogenicity. Regulatory agencies now require rigorous risk assessments and confirmatory testing to ensure product safety, considering all nitrogen atom alert groups. In this study, we present a novel strategy that combines the nitrosation assay procedure (NAP) with 15 N-enriched nitrosating reagents and 15 N NMR spectroscopy to detect and characterize nitrosamine formation. This method enables qualitative analysis of nitrosamines and provides valuable insight into the nitrosation reactivity of pharmaceutical compounds. The diagnostic chemical shift range for N –NO groups was validated, and the method was applied to a series of known nitrosamines and NDSRIs derived from active pharmaceutical ingredients and intermediates. The 15 N-enriched NAP test proved effective in identifying nitrosamines, even in complex matrices, and distinguishing between isomeric and degradation products. This integrated approach provides a robust and rapid tool for nitrosamine risk assessment and supports regulatory compliance by confirming or excluding nitrosamine formation under stress conditions.
Read the paper
Related studies
- Improving sleep quality leads to better mental health: A meta-analysis of randomised controlled trials
- Tocilizumab in patients with severe COVID-19: a retrospective cohort study
- A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study
- Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study
- Are noise and air pollution related to the incidence of dementia? A cohort study in London, England
- Long COVID symptoms and duration in SARS-CoV-2 positive children — a nationwide cohort study
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.