Residual Solvents Analysis Using an Agilent Intuvo 9000 GC with 8697 Headspace Sampler

Importance of the Topic

Residual solvents are volatile organic compounds that must be controlled in pharmaceutical products to ensure patient safety and regulatory compliance. Analysis according to USP <467> provides a standardized framework for quantifying these impurities. Advancements in headspace GC-FID technology improve throughput, sensitivity and method transferability in quality control laboratories.

Objectives and Study Overview

This application note demonstrates the performance of an Agilent Intuvo 9000 gas chromatograph coupled with an 8697 headspace sampler for residual solvent analysis following USP <467>. The study compares two procedures (A and B) using dual columns to separate class 1, 2A and 2B solvents, assessing system precision, signal-to-noise ratios and chromatographic resolution.

Methodology and Instrumentation

Headspace sampling was performed using the Agilent 8697 sampler, directly interfaced to the Intuvo 9000 GC. Class 1, 2A and 2B solvent standards were prepared at specification limits in ultrapure water. Six milliliter aliquots were equilibrated in 20 mL headspace vials. Parameters mirrored USP <467> guidelines with minor adjustments: vial equilibration at 85 °C for 40 min, loop final pressure set to 4 psi to balance resolution and injection precision, and a 10:1 split ratio with an extended initial oven hold.

Použitá instrumentace

• Agilent 8697 Headspace Sampler
• Agilent Intuvo 9000 GC
• Dual columns: DB-Select 624 UI (30 m×0.32 mm, 1.8 µm) and DB-WAX UI (30 m×0.32 mm, 0.25 µm)
• Dual FID detectors including D2 accessory
• Helium carrier gas, nitrogen makeup and vial pressurization gas

Main Results and Discussion

Both procedures achieved excellent retention time (<0.1% RSD) and peak area precision (<4% RSD) across all solvents. Class 1 sensitivity objectives (signal-to-noise >=5) were exceeded. Chromatographic resolution of critical pairs (e.g. acetonitrile/methylene chloride and methylisobutylketone/cis-1,2-dichloroethene) surpassed USP thresholds. The optimized split ratio and oven program enhanced resolution without compromising sensitivity. No coelutions were observed in class 2B analysis, confirming robust separation.

Benefits and Practical Applications

• Simplified method transfer between Agilent 8697 and legacy 7697A samplers
• Reduced cycle times with minimal parameter adjustments
• High precision and sensitivity for regulatory compliance
• Scalable solution for pharmaceutical QC and R&D laboratories

Future Trends and Opportunities

Further integration of automated headspace workflows and data analytics will enhance throughput and data integrity. Emerging detectors and microfluidic GC technologies may offer even faster analysis and lower detection limits. Expansion to other regulated matrices, such as biopharmaceuticals and food products, could leverage similar headspace-GC methodologies.

Conclusion

The Agilent Intuvo 9000 GC coupled with the 8697 headspace sampler meets and exceeds USP <467> requirements for residual solvent analysis. The dual-column, dual-FID configuration delivers reliable precision, sensitivity and chromatographic performance, enabling streamlined implementation in pharmaceutical QC environments.

Reference

1. United States Pharmacopeia USP<467> Residual Solvents.
2. ICH Q3C(R8) Guideline for Residual Solvents.
3. Agilent Technologies Application Note 5991-9029EN on Intuvo 9000 GC.
4. Agilent Technologies Application Note 5990-7625EN on 7697A Headspace Sampler.
5. Agilent Technologies Technical Overview 5991-5182EN.