Dear Lucas Sir,
As per my knowledge, as sertraline alpha carbon have non-aromatic ring and alpha carbon part of ring. Hence, AF-score, we have to consider non-aromatic ring and alpha carbon part of ring also.
Please let me know for clarity.
As cycline, case mentioned below:
Dear @sandeep0315,
N-nitroso-sertraline is included as EMA Example 7. It clearly shows alpha carbon which is part of the ring and bonds to an aromatic ring is considered one of Activating Features.
As far as the case of the cycline, deactivating feature “hydroxyl group bonded to β-carbon*** on only one side of N-nitroso group (cyclic or acyclic)” has the footnote of “***β-Carbon must be in an sp3 hybridization state for this feature to apply.” Therefore OH in cycline compounds is not considered as the deactivating feature.
Thank you sir, for your prompt reply and updating my knowledge
Regard,
Sandeep Bind
Hi Dinkar,
USFDA recently released the guidance on 4-Aug-23 titled “Recommended Acceptable Intake Limits for Nitrosamine Drug Substance Related Impurities (NDSRIs)” in which CPCA approach is defined. Additionally, updated NDSRI information is posted on FDA webpage wherein AI has been defined for 247 NDSRIs as per CPCA approach. Please refer link: Updated Information | Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (NDSRIs) | FDA
Thank you,
Regards
Reena Singh
Thank you very much for clarifying my doubt @Yosukemino
Requesting to help for same
thanks alot Dr. nir its good tools
Dear all,
Great tool! Thanks.
Regarding the α-hydrogen score (table 2 in EMA Q&A, table A in FDA guideline), I am not sure I understand and interpret correctly the note for the first row: “A score of 3 applies when the methylene α-carbon is not part of an ethyl group. If the methylene α-carbon is part of an ethyl group, a score of 2 should be applied”.
Do they mean unsubstituted ethyl group only? For example I have a substituted ethylether next to nitroso group, would that give a score of 2 or 3?
Many thanks in advance for your help.
Thank you for asking.
Do they mean unsubstituted ethyl group only? For example I have a substituted ethylether next to nitroso group, would that give a score of 2 or 3?
It means only the unsubstituted ethyl group. The ethyl ether next to the nitroso group gives a score of 3. The following calculator may be helpful for using CPCA.
great, thanks a lot for your answer!
Very useful one and easy to calculate potency score of any NDSRI.
Thank you @lucas10mauriz and @Yosukemino for the great work. Really appreciated!
this was exactly what i was thinking and it would be really very helpful!!
thanks a lot
Great work and much appreciated. The tool is very useful and definitely generates exciting hope for efficient control going forward. 
Very good initiation. Highly appreciated.
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