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.
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Thank you sir, for your prompt reply and updating my knowledge
Regard,
Sandeep Bind
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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
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- Is the CPCA tool can be used for other than NDSRI impurity??
- Is MeNP Impuirty of Rifampicin is NDSRs??
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!
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Very useful one and easy to calculate potency score of any NDSRI.
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this was exactly what i was thinking and it would be really very helpful!!
thanks a lot
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Great work and much appreciated. The tool is very useful and definitely generates exciting hope for efficient control going forward. 
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Very good initiation. Highly appreciated.
thank you very mach，
Hi, including potency score for one of the NDSRI as provided in pic above, could anyone guide on correctness specially for N-nitroso group in a 5-or6 membered ring as this does not includes the examples provided in USFDA guidance.
thanks in advance
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Thank you for asking, @vinay.singh. Your calculation looks correct. Please check the example in EMA Appendix 2.
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Thank you so much for your comments & confirmation on correctness.
We really appreciate the work done by you and your team.
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