in my opinion, the thiol groups was much more reactive than the secondry amine in the nitrosation. how can we obtain the N-nitroso-bicisate by the organic synthesis
Have you tried performing the 3 nitrosation experiments recommended by the IQ/EFPIA?
https://pubs.acs.org/doi/10.1021/acs.oprd.3c00084
If the N-nitrosamine does not form under these harsh conditions, there is a very fair chance that it may never form in the actual manufacturing/storage conditions.
Having said that, I am aware of some modifications being done to the nitrosation procedures like adding an organic co-solvent such as acetonitrile or dimethylformamide to obtain the N-nitrosamine impurities. But isn’t this a sort of academic research rather than a true risk assessment (considering your actual manufacturing conditions) unless you are a supplier of these nitrosamine impurities?
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