my question maybe basic for some but I am little confused about it.
Azathioprine structure is below.
the nitrosamine risk assessment report from API manufacturer showed that;
No sodium nitrite or any other nitrite is used in the manufacturing process of azathioprine, and No secondary or tertiary amines or quaternary ammonium salts or amide solvents are used in the
manufacture of azathioprine.
and concluded that (Therefore, there is no risk of nitrosamine contamination).
I don’t agree with this conclusion I think there is high risk of nitrosamine impurities formation since the nitrile and the amine both present in the structure of Azathioprine.
am I right or should I accept the nitrosamine risk assessment report conclusion?
I am not experet in chemical reactions, however with quick exploration availble assessment reports of Azathioprine, I foun the below usefull assessment report.
I’d agree that the presence of nitrate as a functional group is a potential concern, as it is in ranitidine and nizatidine; however, unlike in those two drugs, all the nitrogens in this are in aromatic systems, not free amines. While it is possible these could be nitrosated there is minimal chance of a diazonium being formed from these - if mutagenic they act via a different, non-CoC mechanism (ironically, it is related to that by which aromatic nitro groups can be mutagenic!) - and it can be argued these are outside the cohort of concern as a result. See my paper from earlier this year for more details on the aromatic N-nitroso compounds: https://pubs.acs.org/doi/10.1021/acs.oprd.3c00008
There is therefore no relevant NDSRI that can be formed from this API, and assuming the manufacturers are correct that there is no use of amines, the chance of nitrosamines seems small. Note that I haven’t accepted, by comparison, their statement about a lack of nitrite meaning a lack of nitrosating agent; as we’ve recently seen, even the levels of pollution in the air when excipients and DPs are being manufactured has an impact!