This is a ready-to-use calculation worksheet. Replace every <<FILL: ...>> placeholder, confirm every published acceptable-intake figure against the current guidance before use, and route the completed worksheet through your normal technical review. A filled specimen follows.
Section 1: Identify the nitrosamine and applicable acceptable intake
| Field | Entry |
|---|---|
| Nitrosamine identified | <<FILL: name / structure reference>> |
| Is this a “classic” nitrosamine with a published compound-specific AI (e.g. NDMA, NDEA), or a novel NDSRI? | <<FILL>> |
| If compound-specific AI is published: cite the figure and its source | <<FILL: e.g. "NDMA, 96 ng/day, FDA guidance current revision">> |
| If no compound-specific AI: proceed to Section 2 (CPCA) |
Section 2: CPCA categorization (when no compound-specific AI exists)
| Field | Entry |
|---|---|
| Number and position of alpha-hydrogens at the N-nitroso center | <<FILL>> |
| Activating structural features present (e.g. adjacent ether oxygen, aromatic ring, additional amine) | <<FILL>> |
| Deactivating structural features present (e.g. electron-withdrawing group, steric bulk) | <<FILL>> |
| Assigned potency category (PC1-PC5) | <<FILL>> |
| Rationale for the assignment | <<FILL: reasoned narrative, reviewed by Toxicology>> |
Reference AI by category (confirm current values before use): PC1, 18 ng/day (FDA) or 26.5 ng/day (other regions); PC2, 100 ng/day; PC3, 400 ng/day; PC4, 1500 ng/day; PC5, 1500 ng/day.
| Field | Entry |
|---|---|
| Default AI from category | <<FILL: ng/day>> |
| Was the default challenged with an enhanced Ames test or read-across argument? | <<FILL: Yes/No; if Yes, attach the study/argument reference>> |
| Final AI adopted | <<FILL: ng/day>> |
Section 3: Less-than-lifetime (LTL) adjustment, if applicable
| Field | Entry |
|---|---|
| Is the treatment duration genuinely less than lifetime? | <<FILL: Yes/No>> |
| Documented maximum treatment duration | <<FILL: e.g. "up to 12 months", with the clinical/labeled basis>> |
| LTL-adjusted AI (per current M7 staged-duration table) | <<FILL: ng/day>> |
| AI used for the calculation below | <<FILL: lifetime AI or LTL-adjusted AI>> |
Section 4: Product-specific concentration limit
| Field | Entry |
|---|---|
| AI used (ng/day) | <<FILL: A>> |
| Maximum daily dose (g/day) | <<FILL: B>> |
| Product-specific limit = A / B, expressed as ng/g (= ppb) | <<FILL: calculated value>> |
Section 5: Analytical method fit-for-purpose check
| Field | Entry |
|---|---|
| Method used | <<FILL: LC-MS/MS or GC-MS/MS method ID>> |
| Validated limit of quantitation (LOQ) | <<FILL: ppb>> |
| Is LOQ below the product-specific limit calculated in Section 4? | <<FILL: Yes/No; if No, the method cannot support this control, escalate>> |
Section 6: Result vs. limit
| Field | Entry |
|---|---|
| Confirmatory test result | <<FILL: ppb, batch(es) tested>> |
| Result vs. product-specific limit | <<FILL: pass/fail with margin shown>> |
| Preparer | <<FILL: name, date>> |
| Reviewer (Toxicology or Analytical lead) | <<FILL: name, date>> |
| QA approval | <<FILL: name, date>> |
Filled specimen
Section 1. Nitrosamine identified: a novel NDSRI arising from the API’s secondary amine. No published compound-specific AI exists.
Section 2. Two alpha-hydrogens on one side of the nitroso nitrogen, one adjacent electron-donating alkyl ether, no deactivating feature. Assigned category: PC2. Rationale reviewed and signed by Toxicology, 12 August 2026. Default AI from category: 100 ng/day. Default not challenged (no enhanced Ames test commissioned). Final AI adopted: 100 ng/day.
Section 3. Treatment duration is chronic (indefinite, per label). Not less than lifetime. AI used for calculation: 100 ng/day (lifetime, unadjusted).
Section 4. AI used: 100 ng/day. Maximum daily dose: 0.5 g/day (two 250 mg tablets). Product-specific limit: 100 / 0.5 = 200 ng/g = 200 ppb.
Section 5. Method AM-2026-077 (LC-MS/MS). Validated LOQ: 20 ppb. 20 ppb is below 200 ppb: method is fit for purpose.
Section 6. Confirmatory result: 8 ppb across three registered-range batches. Result is well within the 200 ppb limit, with roughly 25-fold margin. Preparer: J. Alvarez, 20 August 2026. Reviewer: Toxicology lead, 21 August 2026. QA approval: R. Nakamura, 22 August 2026.
Common mistakes this worksheet catches
- Adopting a CPCA default without recording the alpha-hydrogen and structural-feature rationale behind the category assignment, leaving a reviewer unable to verify the number.
- Applying a less-than-lifetime adjustment without a documented, defensible treatment-duration basis.
- Comparing a result to the wrong limit because the AI-to-dose arithmetic was done informally rather than shown step by step.
- Accepting a “not detected” result from a method whose LOQ is above the calculated product-specific limit.
How to adapt this worksheet
- Confirm the current published AI figures (compound-specific and CPCA category defaults) against the current FDA and EMA guidance before every use; these values have been revised and could change again.
- If your product’s maximum daily dose varies by indication or population (pediatric vs. adult, for example), run Section 4 separately for each relevant dose.
- Attach this worksheet to the nitrosamine risk assessment record produced by the paired SOP for a complete, traceable file.