Method Development for the Analysis of Residual Solvents and Terpenes in one run using headspace GC-MS/FID

Significance of the topic

In cannabis research and quality control, monitoring both residual solvents and terpenes is critical to ensure consumer safety and product consistency. Regulatory agencies continuously expand lists of controlled solvents and target terpenes, necessitating robust analytical workflows that combine sensitivity, accuracy, and high throughput.

Objectives and overview

This work presents a unified headspace GC-MS/FID method for simultaneous analysis of residual solvents and a broad terpene profile in cannabis and related concentrates. The study aims to reduce analysis time, streamline sample preparation, and deliver reliable quantitation meeting stringent regulatory limits.

Methods and Instrumentation

The proposed workflow integrates an Agilent 7697A headspace sampler, 7890B gas chromatograph, and 5977B mass spectrometer. Key parameters include:

• Headspace equilibration: 20 min at 85 °C, vial shaking level 2
• Injection: loop fill pressure 15 psi, split ratio 20:1, transfer line 100 °C
• GC oven program: initial 35 °C (10 min), ramp 30 °C/min to 180 °C, then 40 °C/min to 260 °C (5 min hold)
• Columns: 30 m × 250 µm DB-624 Ultra Inert; restrictor capillaries for FID and MSD
• Detection: MS in full-scan mode (m/z 30–400) and FID with hydrogen/air makeup gas

Sample prep employs a full evaporation headspace (FET) for plant materials (10–30 mg of ground flower) and liquid standards (10 µL in 20 mL vials). Calibration curves cover 0.5–500 µg/g across eight levels.

Key results and discussion

The method achieved baseline separation of 30+ solvents and over 20 terpenes within a 29-minute cycle. Calibration regressions exceeded r² = 0.999 for representative analytes (e.g., benzene, toluene, limonene, humulene). Limits of quantification were ≤1 µg/g, meeting California action limits. NIST library matching confirmed terpene identities. The dual-detector approach provided orthogonal quantitation, with MS confirming compound identity and FID ensuring robust quantitation for hydrocarbon targets.

Benefits and practical applications

This unified analysis eliminates the need for separate runs, effectively doubling laboratory throughput (2+ samples/hour). It offers:

• Regulatory compliance with USP <467> and state guidelines
• Reduced solvent consumption and instrument wear by consolidating assays
• Accurate quantitation for QA/QC in cannabis production and research settings

Future trends and applications

Emerging directions include application to edible and topical formulations, integration with automated data processing for real-time compliance checks, and expansion to novel terpenoids and emerging processing solvents. Advances in high-resolution MS may further enhance isomer discrimination and trace-level sensitivity.

Conclusion

The developed headspace GC-MS/FID method delivers a fast, reliable, and comprehensive solution for simultaneous analysis of residual solvents and terpenes. By leveraging full-scan MS and FID detection in a single 29-minute run, it addresses throughput and regulatory demands in modern cannabis laboratories.

Reference

• USP <467> Analysis of Residual Solvents. Agilent Technologies Application Note 5991-8032 (2017).
• Firor RL. Analysis of USP <467> Residual Solvents with Improved Repeatability Using the Agilent 7697A Headspace Sampler. Agilent Technologies Application Note 5990-7625 (2012).
• Honnold R, Kubas R, Macherone A. Analysis of Terpenes in Cannabis Using the Agilent 7697A/7890B/5977B Headspace GC-MS System: Faster Analysis Time = Greater Productivity. Application Note 5991-8499 (2017).