Confirmation of THC in Oral Fluids Using High-Resolution 2-D GC/MS

Significance of the Topic

Oral fluid has become a noninvasive alternative to urine for monitoring recent drug exposure. Its resistance to adulteration and straightforward collection make it suitable for roadside, clinical, and workplace testing. Confirming THC at sub-nanogram concentrations ensures reliable forensic and toxicological results.

Objectives and Study Overview

The study aimed to establish a two-dimensional gas chromatography mass spectrometry method capable of confirming THC in buffered oral fluid at a regulatory cutoff of 0.5 ng/mL. By employing heart-cut chromatography and focused trap technology, the method addresses matrix interferences without requiring tandem mass spectrometry.

Used Instrumentation

• Agilent 6890N GC with split/splitless inlet and microfluidic Deans switch
• DB-1ms nonpolar and DB-17ms polar capillary columns (15 m × 0.25 mm × 0.25 μm)
• Air-cooled focusing trap for two-dimensional separation
• Agilent 5975B inert MSD operated in selected ion monitoring mode
• 7683B autosampler module for derivatized sample introduction

Methodology

1. Collect ~400 μL oral fluid and dilute with preservative buffer
2. Screen samples by enzyme immunoassay and select positives for confirmation
3. Add deuterated THC internal standard and perform solid phase extraction
4. Derivatize extracts with BSTFA+TMCS to form TMS derivatives
5. Inject 4 μL onto DB-1ms column; heart cut THC window via timed Deans switch to DB-17ms
6. Cool focusing trap during cut, then rapidly heat to desorb analytes onto second column
7. Acquire SIM data for characteristic THC ions and quantify against a multi-level calibration

Main Results and Discussion

Calibration over 0.2–32 ng/mL exhibited linearity above 0.995. The method achieved an LOQ of 0.2 ng/mL and reliable confirmation at 0.5 ng/mL, with accuracy within 10% and precision below 5% at higher levels. Matrix recovery averaged 70%. Analysis of 20 volunteer samples delivered 100% sensitivity and 94% specificity versus immunoassay. Automated backflush extended column life and reduced maintenance.

Benefits and Practical Applications

The high resolution two-dimensional approach separates THC from co-eluting matrix components without requiring MS/MS, simplifying data review. Heart-cut design lowers background noise, decreases source contamination, and accelerates turnaround. This method is applicable in forensic toxicology, workplace drug testing, and clinical monitoring of cannabis use.

Future Trends and Applications

Further developments may include multi-heart-cut strategies for simultaneous confirmation of multiple drug classes and integration with high resolution mass analyzers for enhanced specificity. Miniaturized microfluidic traps and automated workflows could enable portable confirmatory platforms for on-site testing and real-time compliance monitoring.

Conclusion

High resolution two-dimensional GC/MS with heart cutting and focusing trap technology provides a robust, sensitive, and specific confirmatory method for THC in oral fluid at subnanogram levels. The workflow offers a cost-effective alternative to MS/MS for forensic and clinical laboratories.

References

• James D. McCurry. Using a new gas phase micro fluidic Deans switch for the two dimensional GC analysis of trace methanol in crude oil by ASTM method D7059. Agilent Technologies publication 5989 1840EN.