Fast - GC Method for Residual Solvent Analysis in Drug Discovery Workflow

Significance of the Topic

Pharmaceutical research and development demands rapid, reliable residual solvent analysis to ensure product safety, regulatory compliance, and efficient decision-making in drug discovery workflows. High-throughput methods reduce cycle times and operational costs while maintaining data quality.

Objectives and Study Overview

This application note presents an 8-minute fast gas chromatography method for simultaneous analysis of 46 residual solvents relevant to drug discovery, using the Shimadzu Nexis GC-2030 system. The approach meets ICH Q3C guidelines and supports accelerated process development.

Methodology and Instrumentation

• Instrument: Nexis GC-2030 with AOC-20i autosampler and flame ionization detector (FID)
• Column: Rtx-624, 20 m × 0.18 mm I.D., 1 µm film thickness
• Injection: 0.2 µL split mode (split ratio 200), inlet at 250 °C, high-pressure injection at 100 kPa for 1 min
• Oven program: 42 °C (1.5 min) → 12 °C/min to 72 °C (0.5 min) → 80 °C/min to 240 °C (0.4 min)
• Carrier gas: Helium at 46.6 cm/s linear velocity, 3 mL/min purge flow
• Standards: Solutions in N-methyl-2-pyrrolidone, five-level calibration (10–140% of ICH limits for Class I/II, 5000 ppm for others)
• Precision: Six replicate injections at 100% linearity level
• Automation: Active time management for system start-up, conditioning, and shutdown

Main Results and Discussion

• All solvents exhibited linearity with correlation coefficients ≥ 0.99
• %RSD of peak area at the 100% level remained below 10% for all compounds
• Signal-to-noise ratios at the lowest level exceeded acceptance criteria
• Complete separation of most solvents in under 8 minutes; critical pairs (e.g., acetonitrile/methyl acetate) were identified and addressed

Benefits and Practical Applications

• Enables high-throughput solvent monitoring in early drug discovery
• Reduces carrier gas and energy consumption via automated time management
• Simplifies workflow by covering a broad range of solvent classes in one run
• Supports rapid process optimization and decision-making in pharmaceutical R&D

Future Trends and Applications

Ongoing developments in GC technology are expected to further shrink analysis times, enhance automation, and integrate with laboratory information management systems. Emerging detectors and multidimensional separations may extend sensitivity and solvent coverage, while cloud-based analytics could streamline data interpretation.

Conclusion

The Shimadzu Nexis GC-2030 FID method successfully quantifies 46 residual solvents within an 8-minute run, fulfilling regulatory requirements and meeting the throughput demands of drug discovery workflows. Its robust performance and automated features make it an effective tool for pharmaceutical process development.

References

• ICH Q3C(R8): Guideline for Residual Solvents
• ICH Q2(R2): Validation of Analytical Procedures