Dear Diego,
thanks a lot for your information.
Could you please elaborate a little bit in the modified NAP test you said? Is is relative to the publication of Ashworth?
https://pubs.acs.org/doi/10.1021/acs.oprd.3c00084
After the prformance of the test, how easy was to ‘‘move’’ the sample to the MS system? I am asking because when we have performed the typical NAP test, the sample from the reaction mixture create to us serious problems in our LC-MS/MS system.
To be honest, with the addition of all these compounds in the guidelines, the NAP test could be the first line of ‘‘defense’’, at list to de-risk some of the plausible ‘‘enemies’’ 
thanks
Christos
This is interesting. We need to prepare for these, in . There are good surrogates of these compounds, some well studied. Guanidines nitrosate very easily. Doing a NAP test is helpful but I bet, if you check your product you will find some of the N-nitroso compounds.
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You will find most of N-alkyl guanidines to be positive in NAP test. some carbamates may not be that reactive. Amides are the most elusive. But I know several amides of primary amines that form stable N-nitroso compounds.
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Aloka thanks a lot for your valuable feedback.
according to your experience, the risk could be reasonable if the nitroso-compound is the API in the formulation, or could be a risk even for a relative impurity which could be present in the formulation either from the manufacturing process or from a degradation reaction?
regards
Christos
Interesting, and encouraging, that Health Canada are encouraging the use of ICH M7 as opposed to the nitrosamine guidance - this suggests to me some differentiation of how they should be treated, just as @ASrinivasan and I have argued in our various papers…
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@David, as we both know, like the larger nitrosamines, some of these will be non mutagenic. I think it may be a good idea to do a simple Ames to see how these behave. However, I still think that a bit of pondering, discussion with experts before coming out with this, would have helped. The industry is heavily invested in the nitrosamines. In some cases, products where there are say indole as well as amine groups may have to revisited. Well! the drama doesn’t end. 
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@Chris, we we are tredding on this path, we will have to treat them like the nitrosamines, if there are impurities that can form these N-nitroso compounds, we will need to address them. The question is how we address them. A simple Ames is easy to do. So, if these are Ames positive, may be we try surrogates etc., but here comes the twist, if they are Ames negative, industry should be able to control these at ICH Q3 level.
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thanks a lot Aloka for your feedback. As you say, seems like no ending drama…