FolinicAcidQualityChecker
Folinic Acid
Folinic Acid Quality Checker — Vitamin B9 Analog (Ph. Eur., USP)
ℹ️ The utility checks assay, folic acid (oxidation), specific rotation, dissolution profile.
ℹ️ Does not use machine learning — rule-based logic only.
⚠️ CRITICAL! Folic Acid ≤0.5%. Specific Rotation [-18 to -26]. Dissolution ≥80% in 30 min!
Usage:
FolinicAcidQualityChecker.exe → demo mode
FolinicAcidQualityChecker.exe input.csv output.json → evaluate data
Input format:
BatchNumber,Assay_Percent,pH_Value,Specific_Rotation,Folic_Acid_Percent,Desmethyl_Impurity_Percent,Total_Impurities_Percent,Loss_On_Drying_Percent,Residual_Solvent_Ethanol_ppm,Residual_Solvent_Methanol_ppm,Heavy_Metals_ppm,Dissolution_30min_Percent,Dissolution_60min_Percent,Weight_Variation_RSD,Friability_Percent,Microbial_Count_TAMC,Microbial_Count_TYMC,EColi_Detected,Salmonella_Detected
Example:
FA-SUB-2026-001,99.2,6.5,-22.0,0.2,0.1,0.5,0.3,500,300,6,0.0,0.0,0.0,0.0,20,5,0,0
— WHY IS THIS NEEDED?
Folinic Acid (leucovorin) — reduced form of Vitamin B9, used for folate deficiency or as rescue therapy after methotrexate/5-FU:
• Oxidative degradation: Folinic acid oxidizes easily to folic acid (inactive in this rescue context). Control of folic acid is critical (≤0.5%).
• Chirality: Molecule is chiral. Specific rotation is strictly controlled to confirm stereochemical purity (usually -18° to -26°).
• Solution pH: Critical for molecule stability. Range 4.0–7.0 prevents hydrolysis and oxidation.
• Synthesis may involve ethanol and methanol.
⚠️ CRITICAL:
• Assay: 97.0–103.0%
• pH (10 mg/mL sol): 4.0–7.0
• Folic Acid: ≤ 0.5% (oxidation product)
• Desmethyl Impurity: ≤ 0.5%
• Total Impurities: ≤ 1.5%
• Specific Rotation: -18° to -26°
• Loss on Drying: ≤ 0.5%
• Methanol: ≤ 3000 ppm
• Heavy Metals: ≤ 10 ppm
• Dissolution: ≥ 80% in 30 min, ≥ 85% in 60 min
• Microbiology: standard limits
⚠️ Note: Utility adapted for dissolution profile check. If dissolution data absent (0), check skipped (for substance). For finished forms, deviation from dissolution profile is critical defect. Folic acid control is priority due to risk of therapeutic inefficacy during rescue therapy.
input.csv
BatchNumber,Assay_Percent,pH_Value,Specific_Rotation,Folic_Acid_Percent,Desmethyl_Impurity_Percent,Total_Impurities_Percent,Loss_On_Drying_Percent,Residual_Solvent_Ethanol_ppm,Residual_Solvent_Methanol_ppm,Heavy_Metals_ppm,Dissolution_30min_Percent,Dissolution_60min_Percent,Weight_Variation_RSD,Friability_Percent,Microbial_Count_TAMC,Microbial_Count_TYMC,EColi_Detected,Salmonella_Detected FA-SUB-2026-001,99.2,6.5,-22.0,0.2,0.1,0.5,0.3,500,300,6,0.0,0.0,0.0,0.0,20,5,0,0
URS & FS — user requirements and functional specification
This document defines user requirements and functional specification for the quality-control utility. It supports deployment discussion, IQ/OQ preparation and QC workflow integration.
1. Scope
The Folinic Acid Quality Checker utility is used for Folinic Acid. The actual input.csv is the source of truth for the input structure; control criteria are defined by the executable and the domain description.
The utility does not use machine learning; decisions are produced by deterministic rules.
Categories: Global API expansion
Tags: antivirals, API, biologics, dissolution, essential medicines, global market, heavy metals, impurities, microbiology, oncology, vitamins
2. Execution modes
FolinicAcidQualityChecker.exe → demo mode FolinicAcidQualityChecker.exe input.csv output.json → evaluate data
3. Key controlled areas
- assay / content
- purity and impurities
- dissolution / disintegration
- residual solvents
- microbiology and pathogens
- heavy metals / elemental impurities
- pH and physicochemical parameters
4. Domain limits and critical parameters
- ⚠️ CRITICAL! Folic Acid ≤0.5%. Specific Rotation [-18 to -26]. Dissolution ≥80% in 30 min!
- Oxidative degradation: Folinic acid oxidizes easily to folic acid (inactive in this rescue context). Control of folic acid is critical (≤0.5%).
- ⚠️ CRITICAL:
- Assay: 97.0–103.0%
- pH (10 mg/mL sol): 4.0–7.0
- Folic Acid: ≤ 0.5% (oxidation product)
- Desmethyl Impurity: ≤ 0.5%
- Total Impurities: ≤ 1.5%
- Specific Rotation: -18° to -26°
- Loss on Drying: ≤ 0.5%
- Methanol: ≤ 3000 ppm
- Heavy Metals: ≤ 10 ppm
- Dissolution: ≥ 80% in 30 min, ≥ 85% in 60 min
- Microbiology: standard limits
- ⚠️ Note: Utility adapted for dissolution profile check. If dissolution data absent (0), check skipped (for substance). For finished forms, deviation from dissolution profile is critical defect. Folic acid control is priority due to risk of therapeutic inefficacy during rescue therapy.
5. URS — user requirements
| ID | Requirement | Criticality | Acceptance criterion |
|---|---|---|---|
| URS-001 | The system shall accept an input.csv file for Folinic Acid with the exact columns listed in the “Input data contract” section. | High | A file with the correct header is processed without manual editing; missing mandatory columns produce FAIL/import error. |
| URS-002 | The system shall support execution without arguments in demo mode and execution with input.csv output.json for user data. | Medium | Both execution scenarios produce a predictable result or clear diagnostic error. |
| URS-003 | The system shall perform rule-based controls for: assay / content, purity and impurities, dissolution / disintegration, residual solvents, microbiology and pathogens, heavy metals / elemental impurities, pH and physicochemical parameters. | High | Each controlled parameter receives a status and message; the result does not depend on hidden Excel formulas or ML. |
| URS-004 | The system shall preserve traceability between batch/lot, source values, applied rules and final verdict. | High | Output includes batch identifier, source values, parameter statuses and critical findings. |
| URS-005 | The system shall generate machine-readable output.json for LIMS/ELN/MES, batch record and QA/QC review. | High | JSON contains overall status, check array, warnings, failures and source-file reference. |
| URS-006 | The system shall support use in the client validation package: URS/FS, IQ/OQ preparation, installation and operational scenario checks. | High | The document, test scenarios and reproducible CSV/JSON flow are suitable for audit and internal approval. |
| URS-007 | The system shall clearly separate technical data errors from specification nonconformities. | Medium | Schema/type errors are not mixed with pharmacopoeial deviations and are reported separately. |
6. input.csv data contract
The source of truth for the input schema is the actual input.csv header. Column names are technical identifiers and are not translated.
| # | Column | Type | Unit | Description | Sample | Control rule |
|---|---|---|---|---|---|---|
| 1 | BatchNumber | identifier | as specified | Batch Number | FA-SUB-2026-001 | mandatory field; used for batch/lot traceability |
| 2 | Assay_Percent | decimal | % | Assay % | 99.2 | numeric value; compared with assay/purity limit from specification or method |
| 3 | pH_Value | decimal | pH | p H Value | 6.5 | mandatory numeric value; rule comparison is performed by the utility |
| 4 | Specific_Rotation | decimal | as specified | Specific Rotation | -22.0 | mandatory numeric value; rule comparison is performed by the utility |
| 5 | Folic_Acid_Percent | decimal | % | Folic Acid % | 0.2 | mandatory numeric value; rule comparison is performed by the utility |
| 6 | Desmethyl_Impurity_Percent | decimal | % | Desmethyl Impurity % | 0.1 | numeric value; compared with individual or total impurity limit |
| 7 | Total_Impurities_Percent | decimal | % | Total Impurities % | 0.5 | mandatory numeric value; rule comparison is performed by the utility |
| 8 | Loss_On_Drying_Percent | decimal | % | Loss On Drying % | 0.3 | mandatory numeric value; rule comparison is performed by the utility |
| 9 | Residual_Solvent_Ethanol_ppm | decimal | ppm | Residual Solvent Ethanol ppm | 500 | numeric value; checked as residual solvent against the applicable limit |
| 10 | Residual_Solvent_Methanol_ppm | decimal | ppm | Residual Solvent Methanol ppm | 300 | numeric value; checked as residual solvent against the applicable limit |
| 11 | Heavy_Metals_ppm | decimal | ppm | Heavy Metals ppm | 6 | numeric value; checked as elemental/metal impurity |
| 12 | Dissolution_30min_Percent | decimal | % | Dissolution 30min % | 0.0 | numeric value; dissolution/disintegration profile checked according to method |
| 13 | Dissolution_60min_Percent | decimal | % | Dissolution 60min % | 0.0 | numeric value; dissolution/disintegration profile checked according to method |
| 14 | Weight_Variation_RSD | decimal | as specified | Weight Variation RSD | 0.0 | mandatory numeric value; rule comparison is performed by the utility |
| 15 | Friability_Percent | decimal | % | Friability % | 0.0 | mandatory numeric value; rule comparison is performed by the utility |
| 16 | Microbial_Count_TAMC | decimal | as specified | Microbial Count TAMC | 20 | numeric value; compared with microbiological limits |
| 17 | Microbial_Count_TYMC | decimal | as specified | Microbial Count TYMC | 5 | numeric value; compared with microbiological limits |
| 18 | EColi_Detected | boolean / flag | 0/1 | EColi Detected | 0 | valid flag required; prohibited organisms and growth are normally expected as 0 / absent |
| 19 | Salmonella_Detected | boolean / flag | 0/1 | Salmonella Detected | 0 | valid flag required; prohibited organisms and growth are normally expected as 0 / absent |
CSV example
BatchNumber,Assay_Percent,pH_Value,Specific_Rotation,Folic_Acid_Percent,Desmethyl_Impurity_Percent,Total_Impurities_Percent,Loss_On_Drying_Percent,Residual_Solvent_Ethanol_ppm,Residual_Solvent_Methanol_ppm,Heavy_Metals_ppm,Dissolution_30min_Percent,Dissolution_60min_Percent,Weight_Variation_RSD,Friability_Percent,Microbial_Count_TAMC,Microbial_Count_TYMC,EColi_Detected,Salmonella_Detected FA-SUB-2026-001,99.2,6.5,-22.0,0.2,0.1,0.5,0.3,500,300,6,0.0,0.0,0.0,0.0,20,5,0,0
7. FS — functional specification
| ID | Function | Implementation description |
|---|---|---|
| FS-001 | CLI entry point | The executable FolinicAcidQualityChecker.exe supports demo mode and input.csv output.json processing mode. |
| FS-002 | CSV parser | The import module reads CSV, validates header, column presence/order, value count and encoding. Decimal values are expected with a dot separator. |
| FS-003 | Field conversion | Each column is converted to the expected type: identifier, text, decimal number, date/time or boolean flag. |
| FS-004 | Domain rule engine | For Folinic Acid, explicit rules are applied: range, minimum, maximum, absence of prohibited flag, data completeness or calculation-based check. |
| FS-005 | Criticality handling | Critical violations produce FAIL; non-critical deviations and incomplete data produce WARNING; full conformance produces PASS. |
| FS-006 | JSON writer | output.json stores overall status, per-parameter results, source values, warnings, failures and diagnostic messages. |
| FS-007 | Integration contract | The CSV → JSON format is stable for invocation from LIMS/ELN/MES, scheduled task or wrapper service. |
| FS-008 | Error handling | Schema error, missing file, non-numeric value or JSON write failure returns diagnosable error without silent PASS. |
8. output.json contract
The output file must be suitable for automated processing, audit review and correlation with the source input.csv row.
{
"utility": "FolinicAcidQualityChecker",
"api": "Folinic Acid",
"batchNumber": "FA-SUB-2026-001",
"overallStatus": "PASS|WARNING|FAIL",
"checkedAtUtc": "2026-05-18T00:00:00Z",
"checks": [
{
"parameter": "BatchNumber",
"value": "FA-SUB-2026-001",
"unit": "as specified",
"status": "PASS|WARNING|FAIL",
"message": "Rule-based check result"
},
{
"parameter": "Assay_Percent",
"value": "99.2",
"unit": "%",
"status": "PASS|WARNING|FAIL",
"message": "Rule-based check result"
},
{
"parameter": "pH_Value",
"value": "6.5",
"unit": "pH",
"status": "PASS|WARNING|FAIL",
"message": "Rule-based check result"
},
{
"parameter": "Specific_Rotation",
"value": "-22.0",
"unit": "as specified",
"status": "PASS|WARNING|FAIL",
"message": "Rule-based check result"
},
{
"parameter": "Folic_Acid_Percent",
"value": "0.2",
"unit": "%",
"status": "PASS|WARNING|FAIL",
"message": "Rule-based check result"
},
{
"parameter": "Desmethyl_Impurity_Percent",
"value": "0.1",
"unit": "%",
"status": "PASS|WARNING|FAIL",
"message": "Rule-based check result"
},
{
"parameter": "Total_Impurities_Percent",
"value": "0.5",
"unit": "%",
"status": "PASS|WARNING|FAIL",
"message": "Rule-based check result"
},
{
"parameter": "Loss_On_Drying_Percent",
"value": "0.3",
"unit": "%",
"status": "PASS|WARNING|FAIL",
"message": "Rule-based check result"
}
],
"criticalFindings": [],
"sourceFile": "input.csv"
}9. OQ/PQ test scenarios
| ID | Scenario | Expected result |
|---|---|---|
| TC-001 | Valid CSV with expected header and sample row | All rows are processed; output contains PASS/WARNING/FAIL and parameter-level detail. |
| TC-002 | A mandatory input.csv column is missing | Import is rejected or the row receives FAIL with schema reference. |
| TC-003 | A numeric field contains text or a blank value | Type conversion error is recorded; the result is not hidden as PASS. |
| TC-004 | A parameter is outside specification or critical limit | Critical parameters produce FAIL; non-critical deviations produce WARNING according to the rule. |
| TC-005 | Positive pathogen/microbiological flag or microbiological limit excursion | Critical FAIL is produced with the offending parameter. |
| TC-006 | Insufficient dissolution or excessive disintegration time | FAIL/WARNING is produced according to method criticality. |
| TC-007 | Residual solvent above applicable limit | FAIL is produced with solvent name and measured value. |
10. QA/QC, CSV and change control
- Before production use, the client records executable version, checksum, specification/monograph version, test CSV, expected JSON and IQ/OQ results.
- Column names must not be changed without updating the validator and test scenarios.
- The source CSV, output.json and utility version should be stored together as an evidence package.
- Any change in control rules must go through change control and repeated OQ scenario verification.