Nitrosamines precursors

Hi everyone,

Anyone having idea about possible formation of Nitrosamines from these nitrogen-containing compounds: Hydrazine/ 2-pyrrolidone /N-vinylpyrrolidone ??

Thank you,


I am not chemist, but found paper below on 1,1-dimethylhydrazine and N-aminopiperidine discussing on Aerial oxidation of hydrazines to nitrosamines:

Aerial oxidation of hydrazines to nitrosamines’

There is another paper which I cannot read as it is not free discussing on
Photolysis of nitro hydrazones (from N ,N -disubstituted hydrazines and tetranitromethane) gave nitrosamines.

Nitrosamines from N,N-disubstituted hydrazines

I found also reference of Haydrazine oxidation as potential source of Nitrosamines from Italian Medicines Agnecy in the below link:

This is in answer to question:
Q4 What are the currently identified root causes for
presence of nitrosamines?

Oxidation of hydrazine or other amine-containing functional groups
present in active substances or their impurities/degradants (e.g. from
hydrazones and hydrazides), either in active substance manufacturing
processes or during storage. This root cause has also been observed
during manufacture and storage of finished products containing such
functional groups. Potential oxidants include oxygen and peroxides
(common impurities in some excipients)

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Thank you @m_w_fouad for your feedback and sharing. It’s really helpful.

I assume you are investigating the nitrosating potential of (cross-)povidones, at risk to have the listed contaminants. Povidones are also identified as potential sources of nitrite and formaldehyde contamination next to hydrazine (and maybe of other nitrosation influencers not yet identified). Pinpointing the contribution of povidone to formation of NDSRIs is thus not always straightforward.

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In any case distinction should be made between hydrazine, alkylhydrazines and dialkylhydrazines. The first two categories would not give rise to nitrosamines. Alkylhydrazines (let’s say, phenylhydrazine) upon oxidation become unstable and would degrade releasing N2 gas, as the mechanism would be the same as nitrosation of a primary amine. In fact, the synthesis of phenylhydrazine is carried out by diazotization with sodium nitrite and reduction of the intermediate to form the more stable hydrazine. If you expose phenylhydrazine to an oxidant, you would basically be reverting that last reduction step, and it would end up in degradation.

Dialkylhidrazines are stabilized and cannot undergo this degradation process to release N2 gas, and that is why they can form nitrosamines upon oxidation


I amended my previous answer from “hydrazines” to hydrazine if that is clearer linked to the particular povidone case. Povidone contamination link is hydrazine linked to catalyst byproduct typically (which is what is tested and specified usually), but I didn’t dive in (often also trade secret protected processes) enough to exclude other hydrazines per definition.

If we are talking hydrazines in general, let’s not forget the semi-cyclic ones: still find the 1-amino-4-methylpiperazine case linked to MNP very interesting. Oxidation of hydrazines to nitrosamines is mostly older literature, so interesting to see new cases popping up.


Thank you all for these clarifications. :+1:

Hydrazine (simple hydrazine hydrate or salt) could react with vinyl or amide bond in specific conditions (high concentration and high temperature) but this would not lead to any compound that can further transform to nitrosamine. it could lead to hydrazine amide or N-alkylhydrazine. in the worth case, it could lead to formation of secondary amine (4-(vinylamino)butanehydrazide)