Characterization of Δ8-THC Distillates using Non-Targeted Screening with High Resolution Mass Spectrometry

Importance of Topic

The rise of Delta-8 tetrahydrocannabinol in consumer products has raised safety and regulatory concerns. Although Delta-9 THC is the primary psychoactive component of cannabis, Delta-8 THC is an isomer with similar intoxicating effects produced from hemp derived cannabidiol. The unclear legal framework around synthetic hemp derivatives has spurred market growth for Delta-8 THC distillates. Characterizing reaction byproducts and unknown compounds in these distillates is essential for consumer safety and quality assurance.

Objectives and Overview of Study

This application note demonstrates a non-targeted screening workflow employing ultra performance liquid chromatography coupled with high resolution time of flight mass spectrometry to analyze Delta-8 THC distillates. The study aims to identify known cannabinoids, detect unknown reaction byproducts, and propose elemental compositions and structural relationships. In-house spectral libraries combining authentic standard data and in silico predictions support compound annotation.

Methodology

A mixture of eight cannabinoid standards was diluted to 100 µg/mL in acetonitrile. Distillate samples were prepared at 1 mg/mL. Separation was achieved on a CORTECS C18 column (2.1×100 mm, 1.6 µm) at 25 °C with a formic acid water–acetonitrile gradient. Analysis utilized data independent acquisition (MSe) to collect low and high collision energy spectra from 50 to 1200 Da. Data processing and library searching were performed in UNIFI Scientific Information System, incorporating retention time, accurate mass, isotope pattern, and fragment ion matching.

Instrumentation Used

• Waters ACQUITY UPLC I-Class PLUS
• Waters Xevo G3 QTof mass spectrometer, ESI positive mode
• ACQUITY UPLC PDA detector
• UNIFI software for non-targeted screening and structural elucidation

Main Results and Discussion

Library matching confirmed the presence of Delta-8 THC, Delta-9 THC, exo-THC, cannabidiol, and cannabinol in distillate samples. Several unknown peaks eluting before Delta-8 THC shared a base peak at m/z 315.2318 and proposed formula C21H30O2, suggesting isomeric cannabinoids. Common fragment searching flagged these as structurally related to the C21 neutral cannabinoids. Moreover, in a second distillate sample, an abundant unknown species at m/z 351.2080 corresponded to C21H31ClO2, indicating a monochlorinated cannabinoid analog. Targeted MS/MS experiments confirmed the presence of chlorine isotopes and shared fragment ions with THC isomers.

Benefits and Practical Applications

• Non-targeted screening with MSe reduces false positives by combining precursor and product ion data.
• Custom cannabinoid libraries enhance confidence in identifying known and emerging components.
• Structural elucidation tools such as common fragment and neutral loss searches aid in characterizing unknown reaction byproducts.
• Quality control laboratories can apply this workflow to ensure purity and safety of hemp-derived distillates.

Future Trends and Possibilities

Advancements in high resolution mass spectrometry and expanded spectral libraries will improve detection of low-level impurities and novel cannabinoids. Integration of ion mobility separation and machine learning-based spectral prediction may further streamline non-targeted workflows. Regulatory guidance on synthetic hemp derivatives is expected to evolve, making robust analytical methods critical for compliance and consumer protection.

Conclusion

This study presents a robust workflow for comprehensive analysis of Delta-8 THC distillates. Combining UPLC-QTof MSe acquisition with custom libraries and structural elucidation tools enables identification of known cannabinoids, detection of isomeric byproducts, and discovery of halogenated analogs. Such non-targeted screening approaches are vital for ensuring product quality, understanding complex reaction chemistries, and safeguarding consumer health.

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