According to European Medicines Agency 12 October 2023; EMA/451665/2023
Page-2: Potency categorisation approach does not apply to N-nitrosamines where the N-nitroso group is attached to a nitrogen within a hetero aromatic ring (e.g., nitrosated indole).
Depends on what you are calling the aromatic nitrogen. Molecules like indole, are extremely well known to form nitrosamines. So, may be you can see that if the nitrosation would destroy the aromaticity of the ring, then nitrsamine will not form. If you google, N-nitrosoindole, you will find a lot of data. The most famous example is Nitroso-tryptophan, which is present in beer and other drinks. Similarly N-nitroso imidazole derivatives are well known. By the way, CPCA does not apply to these. You will need to do a true read-across and find a surrogate.
I agree. But the weird thing is that we know so little about the mechanism of nitrosation in solid matrix that we are seeing in finished products, as if we have stepped in a mine field.
So it may be good to check one time if the nitroso-indole is formed it is formed, especially if the pH falls a bit low druing the granulation. However, one has to remember that nitroso-indole is a different class and should not mixed up with nitrosamines. All the current publications on nitrosamines do not apply to it.
Sir, If in the API amine group is present, no nitro group involved in any excipients, but water contains nitrates & nitrites within acceptable limit, then is there any chance of formation of nitrosamines in the finished formulation?