Analysis of USP <467> Residual Solvents using Agilent J&W DB‑WAX Ultra Inert Capillary GC Columns

Importance of Topic

Residual solvents can remain in active pharmaceutical ingredients and final products and impact safety, efficacy and stability. Regulatory bodies require precise control of these solvents to protect patient health and ensure consistent drug quality.

Objectives and Overview of Study

This application note evaluates the performance of Agilent J&W DB-WAX Ultra Inert GC columns under USP 467 procedure B for classes 1, 2A and 2B residual solvents. The work compares single channel HS-GC/FID and a dual channel configuration combining DB-WAX UI and DB-Select 624UI columns to achieve reliable identification and quantification.

Methodology

Samples were prepared according to USP General Chapter 467, with stock solutions in DMSO diluted serially in water and loaded into 20 mL headspace vials. Static headspace sampling was conducted at 85 °C for 40 minutes.

Instrumentation

Agilent 7890B GC with Agilent 7697A Headspace Sampler and FID detection were used. Columns included Agilent J&W DB-WAX Ultra Inert (30 m × 0.32 mm, 0.25 µm) and DB-Select 624UI (30 m × 0.32 mm, 1.8 µm) for dual channel runs. Helium was the carrier gas in constant flow mode.

Key Results and Discussion

The DB-WAX UI column achieved signal-to-noise ratios exceeding USP requirements for class 1 solvents (e.g. benzene S/N greater than 85) and RSDs below 3% for repeatability. Resolution between critical pairs such as acetonitrile and cis-dichloroethene exceeded 1.8. Dual channel analysis allowed simultaneous confirmation on two stationary phases, resolving co-elutions and maintaining high sensitivity and peak shape (for example pyridine tailing approximately 1.02).

Benefits and Practical Applications

• Enhanced inertness and peak symmetry reduce tailing for polar solvents.
• High repeatability and sensitivity meet or exceed USP 467 performance criteria.
• Dual column setup streamlines procedures A and B into a single run, improving laboratory throughput.

Future Trends and Potential Applications

Advances may include integration with mass spectrometry for added specificity, further optimization of headspace parameters to shorten cycle times and expansion to other regulatory methods. Development of more robust inert columns will support analysis of increasingly challenging matrices.

Conclusion

Agilent J&W DB-WAX Ultra Inert columns demonstrate excellent performance for USP 467 residual solvent analysis, providing reliable sensitivity, resolution and repeatability in both single and dual channel GC/FID configurations. This approach enhances laboratory efficiency and regulatory compliance.

Reference

1. USP General Chapter 467 Organic Volatile Impurities, USP 32-NF27, 2009.
2. K. Lynam, Residual Solvent Analysis with Agilent J&W DB-Select 624UI, Agilent Technologies Application Note, 2012.
3. R. L. Firor, Improved Repeatability Using the Agilent 7697A Headspace Sampler, Agilent Technologies Application Note, 2012.
4. System Parameter and Performance Comparison between Agilent 7697A and G1888A Headspace Samplers for USP 467, Agilent Technologies Technical Overview, 2014.
5. B. Tienpont et al., Analysis of USP 467 Residual Solvents using the Agilent 7697A Headspace Sampler with Agilent 7890B GC, Agilent Technologies Application Note, 2013.