is the CPCA approch applicable on 2-methyl-1-nitroso-1H-imidazole?
the 2-methyl-1-nitroso-imidazole could not be synthesizd !Based on the EFPIA workflows for Quality Risk management Jun 2024 v03
can you please explain more about the reason why it will not form? since the supplier of the API has tested this impurity.
Hi,
The CPCA approach cannot be used for nitrosamines formed from nitrogen present in aromatic compounds; in fact, this is explained in Appendix 2 of the EMA.
It is difficult for nitrosamines to form from aromatic compounds because the electron pair participates in the aromaticity of the system (sp2 nitrogen). There are publications on some compounds that cannot be obtained, such as amlodipine (1,4-dihydropyridines). The problem is that there are some nitrosamines from aromatic nitrogens that can be formed, although they are unstable or, in some cases, there are problems with the elucidation of the compound.
Honestly, I do not know if 2-methyl-1-nitroso-1H-imidazole is easy to obtain; it would have to be tested in the lab.
Veeprho has tried to synthesize it without success and sells a document indicating the tests performed:
2-Methyl-1-nitroso-1H-imidazole: Synthesis Attempts and Failure Report (NAP Test) - Veeprho
Regards
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No, but there are surrogates that you can use as this class of nitrosamines are well known.
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nitroso-imidazole if formed is part of Cohort of Concern as nitroso compound but out of scope for N-nitrosamine as defined by agencies