Formaldehyde Catalysis of Nitrosamine Formation

A new paper, published just yesterday.

Investigation of the Formaldehyde-Catalyzed N-Nitrosation of Dialkyl Amines: An Automated Experimental and Kinetic Modelling Study using Dibutylamine - Journal of Pharmaceutical Sciences (

The abstract on this is interesting, especially the influence of formaldehyde at neutral and higher pH levels.

I shall be getting the full copy to digest.


Interesting paper.
The abstract is aligned with some of the principles on this summarized by EMA in an open access paper (equally citing the original Casado work):
Formation of N-Nitrosamine Drug Substance Related Impurities in Medicines: A Regulatory Perspective on Risk Factors and Mitigation Strategies | Organic Process Research & Development (

Historically we had to assess when and if formaldehyde (ppm level LOD/LOQ) testing on medicines was critical to exclude this possible (dominant) root cause (as described in the EMA paper) in nitrosamine pre-testing and post-testing, anyone having to do the same will benefit from buying the paper.


An interesting follow on from this - well worth the hour of your time to watch in my opinion - has given me some areas to ponder.

Hypothesizing on how Nitrosamine Drug Substance Related Impurities (NDSRI’s) are being formed? (


Very interesting, indeed! Thanks for sharing!