N-nitroso acyclovir impurity K

[ccdw]

You added a not too much.
Correct is:
The Carcinogenic Potency Categorisation Approach does apply to N-nitrosamines bearing a carbon atom on both sides of the N-nitroso group where the carbon is not directly double bonded to a heteroatom.
In addition to this “carbon not directly double bonded to a heteroatom” is typically interpreted restrictively, in the sense of nitroso-amide/urea/carbamate/amidine/guanidine functionality sensu stricto and not those patterns being part of a heteroaromatic structure (heteroaromatic classification beats heteroatom-carbon double bond so to say). So you have to judge the aromaticity of the system and the delocalisation of the double bonds and evaluate if the focus should be guanine or guanidine (cf. check of 4n+2 pi-electron rule).

See example of N-nitroso-abacavir in the limit lists.
Same: N-nitroso-maribavir, N-nitroso-rilpivirine impurities, N-nitroso-etravirine.

For discussion on N-nitroso-maribavir and treating guanidine fragments in NDSRIs:

Updated FDA list of published limits

For maribavir, it depends how you define an aromatic bond vs a double bond - the double bond to heteroatom is in an aromatic ring, rather than being a formal double bond, so isn’t perceived as a true double bond in many cheminformatics toolkits, nor does it behave as a guanidine-like structure in this case, which was the intention of the exclusion - to remove the nitrosamide-like structures which can be abiotically hydrolysed to yield diazonium ions from the metabolism-dominated SAR of the CPCA.…

It can be useful to verify CPCA applicability with NDSRIs in the limit list or an automated CPCA tool that has been validated if you have doubts on the aromaticity judgement of model compounds or consistency in the application of the rule heteroaromaticity prior to C=X.