Procedure for Residual Solvent Testing

1) Purpose

The purpose of this SOP is to outline the procedure for determining residual solvent levels in pharmaceutical products to ensure compliance with safety and regulatory requirements.

2) Scope

This SOP applies to all pharmaceutical products within the facility that require residual solvent testing as part of quality control, following pharmacopeial guidelines and regulatory standards.

3) Responsibilities

Quality Control (QC) Department: Responsible for performing residual solvent testing and ensuring compliance with this SOP.
Analytical Laboratory: Responsible for conducting gas chromatography (GC) analysis and interpreting results.

4) Procedure

4.1 Sample Preparation:
    4.1.1 Obtain representative samples of pharmaceutical products requiring residual solvent analysis.
    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 dissolution or extraction methods suitable for residual solvent detection.

4.2 GC Instrument Setup:
    4.2.1 Prepare the GC instrument according to manufacturer instructions and method validation protocols.
    4.2.2 Ensure the GC column is installed, conditioned, and suitable for separating target residual solvents.
    4.2.3 Perform system suitability tests to verify instrument performance and chromatographic resolution.

4.3 Residual Solvent Analysis:
    4.3.1 Inject prepared samples into the GC system using suitable injection techniques (e.g., split, splitless, headspace).
    4.3.2 Program the GC method to include appropriate temperature ramping and detection settings for residual solvent identification.
    4.3.3 Collect chromatographic data and ensure peak integration accuracy for quantification purposes.

4.4 Calibration and Standard Preparation:
    4.4.1 Prepare calibration standards of known residual solvent concentrations covering the required range.
    4.4.2 Inject calibration standards into the GC system to generate calibration curves for each residual solvent.
    4.4.3 Validate calibration curves and adjust method parameters if necessary to ensure accuracy and linearity.

4.5 Calculation of Results:
    4.5.1 Calculate residual solvent concentrations in sample solutions based on peak areas and calibration curves.
    4.5.2 Apply correction factors if applicable (e.g., for sample dilution, recovery efficiency).
    4.5.3 Verify calculations and review results against acceptance criteria specified in pharmacopeial standards or internal specifications.

4.6 Quality Assurance and Validation:
    4.6.1 Document all GC method parameters, sample preparations, and analytical results in the Residual Solvent Testing Report.
    4.6.2 Conduct method validation studies to demonstrate the accuracy, precision, specificity, and sensitivity of the residual solvent testing method.
    4.6.3 Review validation data and ensure compliance with regulatory requirements before releasing test results.

4.7 Documentation:
    4.7.1 Record all residual solvent testing procedures, chromatograms, calibration data, and interpretations in the Residual Solvent Testing Report.
    4.7.2 Maintain detailed records of sample details, GC method validations, instrument maintenance logs, and analyst training records.
    4.7.3 Review and approve the documentation by QC Manager.

5) Abbreviations, if any

QC: Quality Control
GC: Gas Chromatography

6) Documents, if any

Residual Solvent Testing Report
GC Method Validation Protocol and Report
Calibration Curve Records

7) Reference, if any

USP General Chapter <467> – Organic Volatile Impurities
ICH Q3C(R5) – Residual Solvents in Pharmaceuticals

8) SOP Version

Version 1.0