Nitrosamine Limits Calculator
Work out the CPCA potency category and acceptable intake of a nitrosamine drug substance-related impurity, convert it to a ppm limit and check your results.
- FDA and EMA CPCA
- ppm limit
- Several nitrosamines
- No sign-up
Four steps, or fewer
- Choose CPCA for an NDSRI without compound-specific data, or enter a published AI (e.g. NDMA 96 ng/day).
- For CPCA, describe the structure around the N-nitroso group: α-hydrogens and the listed features.
- Enter the maximum daily dose, then optionally paste measured results in ppm.
Not sure what to enter? Press Load example to see the calculator with realistic data. Your inputs are saved in this browser, so they are still there when you come back.
How the CPCA works
The Carcinogenic Potency Categorization Approach predicts the potency of an NDSRI from its structure. NDSRIs without enough α-hydrogens, or with a tertiary α-carbon, go to Category 5. Otherwise a potency score is the sum of the α-hydrogen score and any deactivating or activating features.
| Potency score | Category | AI, ng/day |
|---|---|---|
| ≤ 1 | 1 | 26.5 (FDA) · 18 (EMA) |
| 2 | 2 | 100 |
| 3 | 3 | 400 |
| ≥ 4 | 4 | 1500 |
| Structural rules | 5 | 1500 |
Several nitrosamines: Σ (result / limit) ≤ 1
The CPCA does not cover N-nitrosamides, N-nitrosoureas, N-nitrosoguanidines, N-nitroso groups in aromatic rings, or NDSRIs with more than two N-nitroso groups. Published AIs for specific nitrosamines (in the FDA and EMA lists) take precedence over the CPCA. Check the current lists before use, as they are updated often.
References
- FDA Guidance: Recommended acceptable intake limits for nitrosamine drug substance-related impurities (2023)
- EMA Questions and answers on nitrosamine impurities, Appendix 1 and 2
- ICH M7(R2) Assessment and control of DNA reactive (mutagenic) impurities
These calculators are decision support for orientation and training. They are not validated GMP software, and results must be checked against your approved method, SOP and the current pharmacopoeia or guideline before use in GMP records. Your data is processed in your browser and is not sent to Molgenium.