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<p>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<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-THC) and CBN CRM candidates. Quantification of cannabinoids was performed by <sup>1</sup>H&#xa0;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<sup>9</sup>-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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月10日

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  • 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

摘要

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.

Graphical Abstract