direct injection gas chromatography techniques.

3. Responsibilities

• QC Analyst: Prepare samples, standards, and run GC analysis as per validated method.
• QC Reviewer: Verify chromatograms, peak integration, and calculated values against limits.
• QA Officer: Ensure compliance with documentation and data integrity requirements.

4. Accountability

The QC Head is accountable for ensuring timely and accurate testing of residual solvents, proper qualification of GC instruments, and training of analysts.

5. Procedure

5.1 Sample and Standard Preparation

1. Prepare standard solutions using certified residual solvent reference standards as per STP.
2. Prepare sample solutions using suitable diluent (e.g., DMSO, DMF, water) under specified conditions.
3. Use headspace vials for volatile solvent extraction; seal with crimp caps.

5.2 Instrument Setup

1. Use qualified GC system equipped with FID or TCD detector and headspace or autosampler.
2. Check the following:
   • Column: Capillary column suitable for residual solvent separation
   • Carrier gas flow rate and pressure
   • Oven temperature program as per method
   • Injection volume and split ratio

5.3 System Suitability

1. Run system suitability test using standard mixture.
2. Acceptance criteria:
   • Resolution ≥ 1.5 between critical pairs
   • RSD of peak area ≤ 15% for replicate injections
   • Retention time repeatability within ±5%

5.4 Sample Analysis

1. Inject the sample solution as per sequence defined in the test method.
2. Record chromatograms and identify residual solvent peaks based on retention times.
3. Quantify using external standard calibration or area normalization method.

5.5 Calculation and Reporting

1. Calculate concentration of each solvent using calibration curve or response factor.
2. Compare against ICH Q3C and pharmacopoeial permissible limits (Class 1, 2, or 3 solvents).
3. Report result as:
   • Below detection limit (BDL) if peak not observed
   • Pass/Fail based on specification compliance

5.6 Disposal and Cleanup

1. Dispose residual solvent standards, sample remains, and headspace vials as per hazardous waste SOP.
2. Clean GC injection port, liner, and column after analysis if contamination is suspected.

6. Abbreviations

• GC: Gas Chromatography
• FID: Flame Ionization Detector
• TCD: Thermal Conductivity Detector
• BDL: Below Detection Limit
• LOD: Limit of Detection
• LOQ: Limit of Quantification
• QA: Quality Assurance
• QC: Quality Control

7. Documents

1. Residual Solvent Testing Worksheet (Annexure-1)
2. System Suitability Checklist
3. Sample Preparation Logbook

8. References

• ICH Q3C – Impurities: Guideline for Residual Solvents
• USP <467> – Residual Solvents
• 21 CFR Part 211 – US FDA GMP Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Residual Solvent Testing Worksheet

Date	Sample Name	Batch No.	Solvent	Result (ppm)	Limit (ppm)	Status
13/04/2025	API-A	API-20250413	Methanol	220	300	Pass
13/04/2025	API-A	API-20250413	Toluene	BDL	890	Pass

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial SOP Issue	Regulatory Requirement	QA Head
13/04/2025	2.0	Included headspace mode and disposal steps	Audit Observation	QA Head