Procedure for Water Content Determination (Karl Fischer)

1) Purpose

The purpose of this SOP is to outline the procedure for accurately determining the water content in pharmaceutical substances and products using the Karl Fischer titration method.

2) Scope

This SOP applies to all pharmaceutical substances and products within the facility that require water content determination using the Karl Fischer titration method as part of quality control.

3) Responsibilities

Quality Control (QC) Department: Responsible for performing water content determination and ensuring compliance with this SOP.
Analytical Laboratory: Responsible for conducting Karl Fischer titration and reporting accurate results.

4) Procedure

4.1 Sample Preparation:
    4.1.1 Obtain representative samples of pharmaceutical substances or products requiring water content determination.
    4.1.2 Ensure samples are properly labeled with batch numbers, dates, and any other relevant information.
    4.1.3 Prepare samples according to specified procedures, including weighing and appropriate dissolution or extraction.

4.2 Karl Fischer Reagent Preparation:
    4.2.1 Prepare Karl Fischer reagent following manufacturer instructions and quality control procedures.
    4.2.2 Ensure the reagent is standardized and properly stored to maintain accuracy and reliability.
    4.2.3 Perform necessary checks to verify reagent integrity and titration performance.

4.3 Titration Setup:
    4.3.1 Calibrate the Karl Fischer titrator using standard solutions of known water content.
    4.3.2 Set up the titration vessel with appropriate accessories, electrodes, and stirring apparatus.
    4.3.3 Ensure all connections are secure and free from leaks to prevent moisture ingress during titration.

4.4 Titration Procedure:
    4.4.1 Weigh a precise amount of sample into the titration vessel and record the initial weight.
    4.4.2 Add Karl Fischer reagent to the sample and initiate titration under controlled conditions.
    4.4.3 Monitor titration progress and endpoint detection using suitable detection methods (e.g., electrometric, visual color change).
    4.4.4 Record the volume of reagent required to reach the titration endpoint.

4.5 Calculation of Water Content:
    4.5.1 Calculate the water content in the sample based on the volume of Karl Fischer reagent used and the sample weight.
    4.5.2 Apply correction factors if applicable (e.g., for sample moisture correction, reagent blank correction).
    4.5.3 Validate calculations and ensure results are within acceptable limits.

4.6 Validation and Quality Assurance:
    4.6.1 Perform system suitability tests and method validation according to established protocols.
    4.6.2 Document and review validation results to ensure compliance with regulatory requirements.
    4.6.3 Implement corrective actions for any deviations or out-of-specification results.

4.7 Documentation:
    4.7.1 Record all Karl Fischer titration procedures, results, and observations in the Water Content Determination Report.
    4.7.2 Maintain detailed records of sample details, titration conditions, reagent preparations, and validation data.
    4.7.3 Review and approve the documentation by QC Manager.

5) Abbreviations, if any

QC: Quality Control

6) Documents, if any

Water Content Determination Report
Karl Fischer Reagent Preparation Records
Method Validation Protocol and Report

7) Reference, if any

USP General Chapter <921> – Water Determination
Pharmacopeial standards for Karl Fischer Titration in Water Content Determination

8) SOP Version

Version 1.0