Analysis of residual solvent

Importance of Residual Solvent Analysis

Residual solvents are volatile chemicals used during manufacturing that may remain in trace amounts within final products. Accurate analysis of these compounds is crucial for ensuring product safety, meeting regulatory standards, and protecting human health.

Study Objectives and Overview

This work demonstrates a simultaneous headspace GC–MS method for quantifying Class 1, Class 2A, and Class 2B residual solvents in a single run. Utilizing Shimadzu’s HS-20 sampler and GCMS-QP2010 Ultra with a SH-I-624Sil MS column, the study aims to streamline solvent profiling across diverse chemical classes.

Methodology

Samples were equilibrated at 80 °C for 60 minutes and pressurized before transfer to the GC–MS system. The headspace sampler parameters and GC oven program were optimized to achieve baseline separation of 27 solvent analytes.

Used Instrumentation

• Headspace sampler: Shimadzu HS-20
• Gas chromatograph–mass spectrometer: GCMS-QP2010 Ultra
• Capillary column: SH-I-624Sil MS (30 m × 0.25 mm I.D., 1.40 µm df)
• Headspace conditions: loop mode (1 µL), sample line 150 °C, transfer line 150 °C, gas pressure 100 kPa, equilibration 60 min
• GC settings: split injection (1:30), constant linear velocity at 35 cm/s, oven program 40 °C (20 min) → ramp 10 °C/min → 240 °C (20 min)
• MS settings: ion source 200 °C, interface 250 °C, scan m/z 29–200

Key Results and Discussion

The developed method achieved clear separation of all 27 target solvents within a 35-minute runtime. Chromatograms showed distinct, reproducible peaks for each class without coelution. Sensitivity and repeatability met typical QC requirements, enabling reliable quantification even at low concentration levels.

Benefits and Practical Applications

This approach offers a consolidated workflow for residual solvent screening in pharmaceutical, chemical, and material sciences laboratories. It reduces analysis time, minimizes sample handling, and ensures compliance with ICH and pharmacopoeial guidelines. The robust protocol supports routine quality control and method validation.

Future Trends and Applications

Emerging trends include using advanced stationary phases for faster separations, two-dimensional GC for complex matrices, and integration with automated sample preparation and data analytics. Coupling GC–MS with AI-driven processing could further enhance sensitivity and streamline regulatory reporting.

Conclusion

The presented headspace GC–MS method with the SH-I-624Sil MS column provides an efficient, reproducible, and regulatory-compliant solution for simultaneous analysis of Class 1, 2A, and 2B residual solvents. Its streamlined operation and high resolution make it a valuable asset for modern analytical laboratories.