A novel approach to the production of Δ9-THC and CBN certified reference materials

TL;DR

This paper introduces a new method to produce certified reference materials for Δ9-THC and CBN, improving reliable quantification of cannabinoids in cannabis products.

Contribution

A novel iodine-mediated conversion and isolation strategy enables efficient production of CBN and Δ9-THC reference materials.

Findings

A PULCON-based 1H qNMR method was used to quantify cannabinoids with traceable uncertainties.

An iodine-mediated oxidation process significantly increased CBN yields from cannabis extracts.

Homogeneity and stability studies confirmed the feasibility of producing cannabis-based CRMs.

Abstract

Reliable and traceable quantification of cannabinoids is essential for forensic, regulatory, and quality control applications involving cannabis-derived products. However, the limited availability of certified reference materials (CRMs), particularly for minor cannabinoids such as cannabinol (CBN), remains a major analytical challenge. In this work, an integrated analytical and preparative strategy is presented for the production and characterization of Δ9-tetrahydrocannabinol (Δ9-THC) and CBN CRM candidates. Quantification of cannabinoids was performed by 1H quantitative NMR using the PULCON method, providing traceable mass fraction values with well-defined uncertainties. To overcome the low natural abundance of CBN, a simple iodine-mediated oxidative conversion of Δ9-THC to CBN was developed directly in cannabis extracts, enabling substantial enrichment of CBN and facilitating its subsequent isolation. The impact of this strategy was demonstrated by a more than one order of magnitude increase in isolated CBN yields compared to direct plant-based extraction. The feasibility of producing cannabinoid and plant-based cannabis CRMs was evaluated through homogeneity and transport stability studies conducted within a metrological framework. Overall, this work establishes a practical and metrologically sound framework to produce cannabinoid and plant-based cannabis reference materials, supporting reliable and comparable cannabinoid measurements suitable for forensic and regulatory applications.

The online version contains supplementary material available at 10.1007/s00216-026-06325-4.

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