Characterization of ∆8-THC Distillates Using High Resolution Mass Spectrometry

Significance of the Topic

Delta-8-THC (Δ8-THC) has gained prominence in consumer products despite regulatory ambiguity. As a psychoactive isomer of Δ9-THC, its large-scale production from hemp-derived CBD under harsh conditions yields numerous byproducts. Comprehensive chemical characterization is essential to ensure product safety, regulatory compliance and consumer protection.

Study Objectives

This study aimed to analyze commercial Δ8-THC distillates to:

• Identify known cannabinoids and emerging impurities.
• Propose elemental compositions and structural features of unknown components.
• Evaluate potential halogenated byproducts and assess analytical challenges posed by isomeric mixtures.

Methodology and Instrumentation

Sample Preparation:
Distillates were dissolved in acetonitrile and diluted.

Chromatography and Detection:

• Instrument: ACQUITY UPLC I-Class Plus system.
• Column: CORTECS C18 (2.1×100 mm, 1.6 µm).
• Mobile phases: 0.1% formic acid in water (A) and acetonitrile (B).
• Flow rate: 0.56 mL/min; column temperature: 25 °C; injection: 0.5–1 µL.
• PDA detection: 210–400 nm, data at 228 nm for quantitation.

Mass Spectrometry:

• Instrument: Xevo G3 QToF with UNIFI software.
• Ionization: ESI positive, capillary 1.0 kV, cone 15 V.
• Desolvation: 450 °C, gas flow 100/1000 L/hr.
• Acquisition: MSE mode with simultaneous low CE (4 eV) and high CE (15–45 eV ramp).
• Mass range: m/z 50–1200.
• Data analysis: Library matching of precursor masses, fragments, isotopic patterns, retention times and structural elucidation tools.

Main Results and Discussion

Two commercial Δ8-THC distillates (samples A and B) were profiled.

Identified Components:

• Known cannabinoids: CBD, CBN, exo-THC, Δ9-THC and Δ8-THC confirmed by spectral matching and retention times.

Unknown Neutral Cannabinoid Isomers:

• Multiple components exhibited a base peak at m/z 315.2319, consistent with C21H30O2.
• Proposed to be structural isomers of Δ9-THC; Area% ranged 0.13–4.9% in UV at 228 nm.

Chlorinated Impurity:

• Sample B contained a major unknown at tR 3.11 min (Area% 19.4%) with m/z 351.2080 matching C21H31ClO2 (iFit 99.7%), indicating mono-chlorinated Δ9-THC-like structure.
• MS/MS confirmed common fragment ions with Δ9-THC isomers, highlighting halogenated byproduct formation under synthetic conditions.
• Purity of Δ8-THC in sample B measured at 79%.

Analytical Challenges:

• Complex isomeric mixtures demand high chromatographic resolution and accurate mass fragmentation to avoid misidentification of controlled Δ9-THC.

Benefits and Practical Applications

Comprehensive profiling of Δ8-THC distillates enables:

• Quality control and authenticity verification in cannabis testing laboratories.
• Detection of potentially harmful byproducts, including halogenated species.
• Support for regulatory bodies by distinguishing legal Δ8-THC from regulated Δ9-THC.

Future Trends and Opportunities

Continued development is anticipated in:

• Expanded mass spectral libraries covering synthetic cannabinoids and their halogenated derivatives.
• Targeted MS/MS workflows for rapid screening of novel byproducts.
• Toxicological evaluations of unidentified impurities to inform risk assessments.
• Advanced chromatographic methods and ion mobility to resolve complex isomeric profiles.

Conclusion

UHPLC–PDA coupled with QToF HRMS effectively characterizes Δ8-THC distillates, identifying both expected cannabinoids and unexpected isomeric or halogenated byproducts. This approach enhances understanding of product composition, informs safety assessments, and supports regulatory compliance in the expanding Δ8-THC market.

References

1. Erickson BE. Delta-8-THC craze concerns chemists. C&EN News. 2021;99(31).
2. Hudalla C. We believe in unicorns (and Delta-8). The Cannabis Scientist. 2021.
3. Golombek P, et al. Conversion of CBD into psychotropic cannabinoids including THC: A controversy in the scientific literature. Toxics. 2020;8(2).
4. Kiselak TD, et al. Synthetic route sourcing of illicit at home CBD isomerization to psychoactive cannabinoids using ion mobility-LC-MS/MS. Forensic Sci Int. 2020;308:110173.
5. Watanabe K, et al. Conversion of cannabidiol to Δ9-THC and related cannabinoids in artificial gastric juice and their pharmacological effects in mice. Forensic Toxicol. 2007;25(1):16–21.
6. Meehan-Atrash J, Rahman I. Novel Δ8-THC vaporizers contain unlabeled adulterants, unintended byproducts of chemical synthesis, and heavy metals. Chem Res Toxicol. 2022;35(1):73–76.
7. Webster GRB, Sarna LP, Mechoulam R. US Patent Application US20040143126A1.
8. Helander A, et al. Analytical and medico-legal problems linked to the presence of delta-8-THC: Results from urine drug testing in Sweden. Drug Test Anal. 2022;14(2):371–376.
9. Usami N, et al. Synthesis and pharmacological activities in mice of halogenated Δ9-THC derivatives. Chem Pharm Bull. 1998;46(9):1462–1467.
10. Usami N, et al. Synthesis and pharmacological evaluation in mice of halogenated cannabidiol derivatives. Chem Pharm Bull. 1999;47(11):1641–1645.
11. Morales P, et al. An overview on medicinal chemistry of synthetic and natural derivatives of cannabidiol. Front Pharmacol. 2017;8:422.