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

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 Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and CBN CRM candidates. Quantification of cannabinoids was performed by 1 H 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 Δ 9 -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. Graphical Abstract