Analysis of Residual Solvents in Pharmaceuticals

Analysis of Residual Solvents in Pharmaceuticals using GC-FID on SH-PolarWax Column

Significance of the Topic

Residual solvents are trace organic chemicals used in drug synthesis. Their elimination is critical for patient safety and regulatory compliance. Class 2 solvents, in particular, require sensitive analytical methods to ensure levels remain below prescribed limits.

Aims and Overview

This study outlines a robust gas chromatographic method for simultaneous quantification of eight class 2 solvents in water-soluble pharmaceutical matrices. The objective was to achieve reliable separation and detection in a single run.

Applied Instrumentation

• Gas chromatograph: Shimadzu Nexis GC-2030 with AOC-20i Plus autosampler
• Detector: FID-2030 flame ionization detector
• Column: SH-PolarWax, 30 m × 0.53 mm I.D., 1 µm film thickness
• Carrier gas: Helium, pressure-controlled at 26.6 kPa
• Injection: high-pressure split (1:1), 160 °C, 1 µL injection volume
• Oven program: 50 °C hold 7 min, ramp 4 °C/min to 110 °C, ramp 10 °C/min to 220 °C, hold 20 min
• Detector gases: H2 32 mL/min, air 200 mL/min, He makeup 24 mL/min

Main Results and Discussion

All eight solvents (2-methoxyethanol, 2-ethoxyethanol, N,N-dimethylformamide, N,N-dimethylacetamide, ethylene glycol, N-methylpyrrolidone, formamide, sulfolane) were baseline-resolved within a 53 min run. The temperature program ensured elution of low and high boiling compounds without peak broadening. FID provided consistent sensitivity across analytes.

Benefits and Practical Applications

• Compliance with ICH guidelines for residual solvents
• Simple sample preparation and method setup
• High reproducibility for routine QA/QC workflows
• Adaptability to various water-soluble pharmaceutical formulations

Future Trends and Potential Uses

Advancements may include faster temperature ramps, smaller diameter columns for reduced analysis time, and integration with mass spectrometry for enhanced specificity. Headspace sampling techniques can further streamline solvent analysis.

Conclusion

The described GC-FID method on a SH-PolarWax column offers a reliable, robust approach for quantifying class 2 residual solvents in pharmaceuticals, supporting regulatory compliance and quality assurance.