Efficient Analysis of Residual Solvents in Pharmaceuticals Using the Compact Model, Brevis GC-2050 (2) —JP18 and USP467, Water Insoluble Samples—

Importance of the Topic

Residual solvents in pharmaceutical products pose potential health risks, and strict limits defined in the Japanese Pharmacopoeia (JP18) and US Pharmacopeia (USP) General Chapter 467 require accurate testing. Compact, high-throughput gas chromatography systems help laboratories with limited bench space maintain compliance and productivity.

Study Objectives and Overview

This application note assesses the performance of the Shimadzu Brevis GC-2050 compact gas chromatograph combined with an HS-20 NX headspace sampler for analyzing Class 1 and Class 2 residual solvents in water-insoluble pharmaceutical samples. The study aims to demonstrate pharmacopoeia compliance and laboratory throughput improvements through instrument miniaturization.

Methodology and Instrumentation

• Gas Chromatograph: Brevis GC-2050 with flame ionization detector (FID)
• Capillary Columns: Procedure A uses SH-I-624Sil MS (0.53 mm × 30 m, 3.0 µm), Procedure B uses SH-PolarWax (0.32 mm × 30 m, 0.25 µm)
• Carrier Gas: Helium under linear velocity control at 35 cm/sec
• Temperature Programs: A – 40 °C (20 min) → 10 °C/min → 240 °C (20 min); B – 50 °C (20 min) → 6 °C/min → 165 °C (20 min)
• Headspace Sampler: HS-20 NX with ultra-short transfer line (vial equilibration at 80–105 °C, 45 min)
• Sample Preparation: Water-insoluble samples dissolved in DMF; injection volume 1 mL

Main Results and Discussion

• Class 1 analysis of 1,1-dichloroethane, 1,1,1-trichloroethane, carbon tetrachloride, benzene, and 1,2-dichloroethane produced clear, well-resolved peaks under both procedures.
• Class 2 analysis resolved 22 solvents, including new ICH Q3C (R8) additions tert-butyl alcohol, cyclopentyl methyl ether, and methyl isobutyl ketone; critical peak resolutions exceeded the required 1.0 threshold.
• Chromatographic performance and retention times met JP18 and USP 467 specifications, confirming method robustness on a compact platform.

Benefits and Practical Applications

• Compact footprint reduced by approximately 35% versus conventional GC, enabling more installations and higher throughput in space-constrained labs.
• Full compliance with JP18 and USP 467 ensures regulatory acceptance for pharmaceutical quality control.
• Capability to analyze newly regulated Class 2 solvents broadens application scope for method updates.

Future Trends and Possibilities

Continued instrument miniaturization will support multi-unit deployments in small laboratories. Integration with automated data analysis and laboratory information management systems (LIMS) will streamline workflows. Advances in column technology and rapid temperature programming may further reduce analysis times while maintaining resolution.

Conclusion

The Brevis GC-2050 paired with the HS-20 NX headspace sampler provides reliable, pharmacopoeia-compliant residual solvent analysis for water-insoluble pharmaceuticals. Its compact design enhances laboratory capacity and throughput without compromising performance.

Reference

Shimadzu Corporation Application Note 01-00517-EN, First Edition September 2023