A Consideration of the Extent That Tertiary Amines Can Form N-Nitroso Dialkylamines in Pharmaceutical Products

Dr. Ashworth published an excellent paper to clarify the risk posed by tertiary amines. Now we can overcome nitrosamine contamination risk brought by simple tertiary amine. I appreciate their dedication.



Being a poor consultant, I could not access the paper but the abstract is interesting.
As you know, this topic is my weakness as it was a topic of my PhD advisor’s PhD research :slight_smile: and most of the work on tertiary amine nitrosation was done in our lab.

The issue here is that the studies that show tertiary amine nitrosation are much slower were done in solution phase. Now we are seeing significant amount of nitrosamines in drug product which have tertiary amines as API. One possibility is that the reaction in solid phase is going though a different pathway. Or it could just be that a dosage form is like a reaction vessel where the reaction is happening for two years. So, even if the reaction is slower, we see the nitrosamine.

Again, I have not read the paper yet. Would love to see what is in it.

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