Formation of Dialkyl-N-nitrosamines in Aqueous Solution: An Experimental Validation of a Conservative Predictive Model and a Comparison of the Rates of Dialkyl and Trialkylamine Nitrosation

[Yosukemino]

Thank you for sharing your thoughts, @ASrinivasan. The paper which Moser et. al wrote demonstrated that tertiary amines are less reactive with nitrite in the solid state.

N-Nitrosamine Formation in Pharmaceutical Solid Drug Products: Experimental Observations -Pub

Publication " N-Nitrosamine Formation in Pharmaceutical Solid Drug Products: Experimental Observations" by Moser et al. Link: https://www.jpharmsci.org/article/S0022-3549(23)00028-X/fulltext Abstract: The potential presence of N -nitrosamines in medicinal products has become a matter of concern for health authorities and pharmaceutical companies. However, very little information is available in published literature on N -nitrosamine formation within pharmaceutical drug products. In response,…

I think the simple tertiary amines react with nitrite in the same manner as in the aqueous phase, even in the solid state. On the other hand, for complex tertiary amines, we should consider the reaction on a case-by-case basis.

We should not ignore the risk of nitrosamine formation of tertiary amines without consideration.
I heard NOx gas in the air caused nitrosamine formation during the jet milling of secondary amine API salt. The vulnerable amines are literally “vulnerable” in some cases.