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

**Authors:** Lucas J. de Carvalho, Silvia Regina Pinheiro Lopes, Karine Ecard Cesar, Douglas S. A. Chaves, Lívia C. R. M. da Frota, Neide Mara de Menezes Epifanio, Fernanda Gadini Finelli, Bruno C. Garrido

PMC · DOI: 10.1007/s00216-026-06325-4 · 2026-02-10

## 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.

## Key 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.

## Linked entities

- **Chemicals:** cannabinol (PubChem CID 2543), iodine (PubChem CID 807)

## Full-text entities

- **Chemicals:** iodine (MESH:D007455), CBN (MESH:D002187), 1H (-), cannabinoid (MESH:D002186), Delta9-THC (MESH:D013759)

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12999805/full.md

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Source: https://tomesphere.com/paper/PMC12999805