The effect of nitrite and nitrate presence in raw materials on nitrosamine risk

I would be very pleased if you could share your evaluation and comments on the following subject.

We request nitrosamine risk assessment studies from our raw material suppliers within the scope of drug product nitrosamine risk assessment. Suppliers, especially excipient suppliers, share the results of nitrite and nitrate analysis in the raw materials they produce. What should we consider when evaluating nitrite and nitrate levels of raw materials? What should be the maximum nitrite and nitrate levels in raw materials? What is the importance of nitrate presence in terms of nitrosamine risk?

Thanks in advance.

@Elif Thanks for your question. I suggest doing a search :mag: in the community using the tag ‘Excipient’ so you can see all the discussions that have been happening on the particularity of Excipients in Nitrosamines challenges.

Additionally, 2 posts that illustrate the use of these reported values of Nitrites in examples of risk assessments.

Hi, @Elif. I think this post is also helpful for you to understand the amounts of nitrites in excipients and their contribution to the drug product.

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Thank you very much for your valuable support.

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Thank you very much for your kind respond.

Presence of nitrates and nitrites in excipients, may potential cause of formation of nitrosamine impurities in the drug product if there is secondary / tertiary amine present in any of other component. Same can be confirmed and ruled out after testing of product.
(Addition to this, there are other factors too like acidic environment, chosen mfg. process etc.)
We cannot go by thumb rule for specific level or limits in excipients, chemistry wise needs to confirm the possibility of reaction between available nitrites / nitrates and secondary amines present in other components of drug product.
Hope this may useful.

Really very useful stoichiometric calculations for reaction mechanism between nitrite and Nitrosamine.

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Thank you very much for your response.