INCREASING THE THROUGHPUT OF CANNABINOID PROFILING AND POTENCY DETERMINATION USING CHROMATOGRAPHIC GEOMETRIC SCALING PRINCIPLES

Significance of the Topic

The rapid legalization of cannabis for medical and recreational use has driven a surge in product diversity and volume. Reliable, high-throughput analytical methods are essential for producers, regulators, and consumers to ensure accurate potency and quality control.

Objectives and Study Overview

This study demonstrates the transformation of an isocratic HPLC method for 16 cannabinoids into a UPLC approach using geometric scaling principles. The goal is to double productivity and improve resource efficiency while maintaining chromatographic resolution and regulatory compliance.

Methodology

The original HPLC method conditions (water with 0.1% TFA and acetonitrile isocratic elution) were geometrically scaled to UPLC by adjusting column dimensions, flow rate, and injection volume. The linear velocity ratio (L/dp) was preserved by reducing particle size from 2.7 µm to 1.6 µm and column length from 150 mm to 100 mm. Calibration curves for CBD and Δ9-THC were generated over ten concentration levels (0.004–1.000 mg/mL) to verify linearity and accuracy.

Instrumentation Used

• Waters ACQUITY UPLC H-Class System
• CORTECS UPLC Shield RP18 column (1.6 µm, 2.1 × 100 mm)
• ACQUITY UPLC PDA detector (228 nm, 4.8 nm resolution)
• Empower 3 data acquisition software
• DEA-exempt reference standards from Cerilliant

Main Results and Discussion

The UPLC method achieved baseline separation of all 16 cannabinoids in 10.5 minutes with resolution values (Rs) above 2.0. Compared to the original HPLC approach, UPLC delivered:

• 2.5-fold increase in injections per 24 hours (55 to 140)
• 60% reduction in cycle time (26 min to 10.3 min)
• 87% lower injection volume (5 µL to 0.7 µL)
• 86% solvent savings (52 mL to 7.2 mL per run)

Linearity for CBD and Δ9-THC exhibited R2 ≥ 0.999 across all levels. Overlay chromatograms confirmed method robustness for both high-CBD and high-THC flower and concentrate matrices.

Benefits and Practical Applications

This optimized UPLC protocol provides laboratories with:

• Faster turnaround times for potency testing
• Reduced solvent consumption and waste
• Smaller sample volume requirements
• Scalability for diverse cannabis matrices (flowers, extracts, concentrates)

Future Trends and Potential Uses

Potential developments include:

• Coupling UPLC with mass spectrometry for expanded compound profiling and impurity assessment
• Automated sample preparation to further accelerate throughput and reduce manual labor
• Implementation of process analytical technology (PAT) for real-time monitoring in cultivation and manufacturing
• Adaptation of geometric scaling approaches to emerging cannabis derivatives and novel bioactive compounds

Conclusion

By applying geometric scaling principles, the conversion from HPLC to UPLC doubled analytical throughput and dramatically reduced solvent and sample volume consumption, all while preserving chromatographic performance. This strategy meets the growing need for rapid, reliable cannabinoid analysis.

Reference

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