Useful publications to sharpen your skills for reviewing DS risk assessment

Please keep in mind that conducting a thorough risk assessment is absolutely vital for navigating the complexities of nitrosamines. You cannot simply take your supplier’s word for it when they claim their products are “nitrosamines-free” without providing proper documentation or confirmatory data. Just recently, a Nitrosamines team confidently presented me with a folder filled with declaration letters to prove that their product, Metformin, posed no risk.

I recognize that not every organization has dedicated teams of medicinal or organic chemists readily available to review API synthetic routes or DMFs. However, it’s crucial to revisit and enhance your understanding of organic chemistry. Remember, you’re not alone in this endeavor. Our community offers a wealth of resources and expertise that can provide valuable guidance, but it’s important to take ownership of your learning and not expect others to do the work for you.

Here are great articles from the early days of Nitrosamines that can help you on that journey…

An Organic Chemist’s Guide to N-Nitrosamines: Their Structure, Reactivity, and Role as Contaminants

Access: https://doi.org/10.1021/acs.joc.0c02774

Nitrosamine Reactivity: A Survey of Reactions and Purge Processes

Access: https://doi.org/10.1021/acs.oprd.1c00162

Pathways for N-Nitroso Compound Formation: Secondary Amines and Beyond

Access: https://doi.org/10.1021/acs.oprd.0c00323

Approaches and Considerations for the Investigation and Synthesis of N-Nitrosamine Drug Substance-Related Impurities (NDSRIs)

Access: https://doi.org/10.1021/acs.oprd.3c00084

Potential for the Formation of N-Nitrosamines during the Manufacture of Active Pharmaceutical Ingredients: An Assessment of the Risk Posed by Trace Nitrite in Water

Access: https://doi.org/10.1021/acs.oprd.0c00224

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