Standard Operating Procedure for LOD and Moisture Content Determination in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/127/2025 |
| Supersedes | SOP/API/127/2022 |
| Page No. | Page 1 of 9 |
| Issue Date | 13/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 13/04/2026 |
1. Purpose
To define the procedure for determining Loss on Drying (LOD) and moisture content in Active Pharmaceutical Ingredients (APIs) using both conventional oven method and Karl Fischer titration, ensuring consistency and regulatory compliance.
2. Scope
This SOP is applicable to Quality Control personnel involved in the analysis of LOD and moisture content in raw materials, intermediates, and final APIs
using gravimetric and Karl Fischer techniques.
3. Responsibilities
- QC Analyst: Perform LOD/moisture analysis and record data accurately.
- QC Executive: Review results and ensure compliance with specified limits.
- QA Officer: Audit test procedures and review LOD and KF logbooks.
4. Accountability
The Head – QC is accountable for ensuring that all LOD and moisture determinations are conducted as per validated procedures and recorded in compliance with cGMP.
5. Procedure
5.1 Loss on Drying (Oven Method)
- Calibrate the analytical balance and drying oven before use.
- Dry a suitable weighing bottle (with lid) in oven at 105°C for 30 minutes and cool in desiccator.
- Weigh accurately 1-2 g of sample in the dried bottle (W1).
- Dry the sample at specified temperature (usually 105°C) for 3 hours or as per STP.
- Cool the bottle in a desiccator for 30 minutes and weigh again (W2).
- Repeat drying until constant weight is achieved (not more than 0.5 mg difference).
- Calculate LOD using the formula:
% LOD = ((W1 – W2) / W1) × 100
5.2 Karl Fischer Method (Moisture Content)
- Ensure Karl Fischer apparatus is calibrated with certified water standard.
- Weigh accurately the sample (10–100 mg depending on expected moisture) and transfer to KF titration cell using syringe, septum, or direct introduction.
- Perform blank titration and standardization if necessary.
- Titrate until endpoint is achieved (stable measurement over 30 seconds).
- Record volume of Karl Fischer reagent used and calculate % moisture:
% Moisture = (Volume × Factor × 100) / Sample Weight (mg)
5.3 Acceptance Criteria
- Compare observed results with specification mentioned in STP or pharmacopoeia (e.g., NMT 1.0% for moisture content).
- Document results in LOD/Moisture Content Worksheet (Annexure-1).
5.4 Precautions
- Use tongs/gloves to handle hot containers during LOD analysis.
- Ensure reagents used in KF method are within expiry and moisture-free.
- Keep desiccators tightly closed when not in use.
6. Abbreviations
- LOD: Loss on Drying
- KF: Karl Fischer
- STP: Standard Test Procedure
- API: Active Pharmaceutical Ingredient
- QA: Quality Assurance
- QC: Quality Control
7. Documents
- LOD and Moisture Content Worksheet (Annexure-1)
- KF Calibration Log
- Drying Oven Calibration Record
8. References
- USP <921> – Water Determination
- ICH Q6A – Specifications: Test Procedures and Acceptance Criteria
- 21 CFR Part 211 – US FDA GMP
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: LOD and Moisture Content Worksheet
| Date | Sample Name | Batch No. | Method | Result (%) | Limit | Status |
|---|---|---|---|---|---|---|
| 13/04/2025 | API-XY | API-20250413 | KF | 0.84% | NMT 1.0% | Pass |
| 13/04/2025 | API-ZA | API-20250412 | LOD | 1.15% | NMT 1.5% | Pass |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial SOP Issue | New Procedure | QA Head |
| 13/04/2025 | 2.0 | Included KF method and moisture-specific precautions | Annual Review | QA Head |