Standard Operating Procedure for Water Content Determination in Elixirs Using Karl Fischer Titration
| Department | Elixir Department |
|---|---|
| SOP No. | SOP/ELX/228/2025 |
| Supersedes | SOP/ELX/228/2022 |
| Page No. | Page 1 of 8 |
| Issue Date | 11/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 11/04/2026 |
1. Purpose
To establish a standard procedure for the determination of water content in elixir formulations using the Karl Fischer (KF) titration method, ensuring accurate and consistent moisture analysis in accordance with pharmacopeial and regulatory standards.
2. Scope
This SOP is applicable to the Quality Control Department for routine testing of water content in elixirs during release and stability testing using volumetric or coulometric KF titration.
3. Responsibilities
- QC Analyst:
- Prepare and analyze samples using the Karl Fischer method.
- Ensure all data is accurately recorded in the logbook and BMR.
- QC Supervisor:
- Verify calibration status of the KF instrument and review results.
- QA Officer:
- Ensure test compliance with specifications and regulatory requirements.
4. Accountability
The QC Head is accountable for execution and validation of the KF analysis. The QA Head is responsible for ensuring regulatory compliance and final disposition based on moisture
results.
5. Procedure
5.1 Equipment and Materials
- Karl Fischer Titrator (volumetric or coulometric type)
- KF reagent (methanol-based or compatible with solvent system)
- KF oven (for samples with interference, if required)
- Syringe with needle for injection
- Analytical balance (calibrated)
5.2 System Setup and Calibration
- Ensure the instrument is calibrated using sodium tartrate dihydrate or water standards.
- Check the reagent factor prior to each batch analysis.
- Perform blank titration and set to zero before analysis.
5.3 Sample Preparation
- Weigh accurately about 1–2 g of elixir formulation into a clean, dry syringe.
- Inject directly into the KF cell if compatible. For samples with high alcohol or sugar content, use KF oven technique as required.
5.4 Titration Procedure
- Inject sample and start the titration automatically.
- Allow the endpoint to be detected automatically.
- Record the amount of water detected in mg or percentage.
- Repeat in duplicate. Report the average value.
5.5 Calculations
% Water Content = (mg H2O / Sample Weight in mg) × 100
5.6 Acceptance Criteria
- The water content must fall within the specified limit in the product specification (e.g., NMT 5.0%).
- Any value beyond specification should trigger an investigation.
5.7 Documentation
- Record all readings in the Water Content Test Logbook (Annexure-1).
- Attach titration printouts and maintain with the respective BMR.
- Enter KF reagent batch number, expiry, and calibration details.
6. Abbreviations
- SOP: Standard Operating Procedure
- KF: Karl Fischer
- QC: Quality Control
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
7. Documents
- Water Content Test Logbook (Annexure-1)
- Instrument Calibration Log
- Batch Manufacturing Record (BMR)
8. References
- USP Chapter <921> – Water Determination
- Ph. Eur. 2.5.32 – Water: Karl Fischer Method
- ICH Q2(R1) – Validation of Analytical Procedures
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Water Content Test Logbook
| Date | Batch No. | Sample Weight (mg) | Water Found (mg) | % Water | Reagent Batch No. | Tested By | Verified By |
|---|---|---|---|---|---|---|---|
| 11/04/2025 | ELX-0425-046 | 1000 | 34.2 | 3.42 | KF-9823 | Rajesh Kumar | Sunita Reddy |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2024 | 1.0 | Initial SOP Release | New SOP Creation | QA Head |
| 11/04/2025 | 2.0 | Included oven method and calculation clarity | Method Enhancement | QA Head |