Analytical determination of cannabinoids in Cannabis Sativa L.: the key role of boric acid complexation

The electrochemical discrimination of cannabinoids remains a major challenge in electroanalytical sensing due to their structural similarity and overlapping redox behaviour. This study demonstrates that boric acid enables the selective detection of acidic cannabinoids Δ9-tetrahydrocannabinolic acid (Δ9-THCA) and cannabidiolic acid (CBDA) through the formation of an intramolecular borate chelate. At neutral pH, boric acid forms a tetrahedral borate complex through anchoring at the carboxylate group and coordination at the phenolic oxygen, stabilizing a six-membered metallacycle. This complexation induces distinct analytical signatures, including the emergence of a high-potential oxidation peak in differential pulse voltammetry, a blue-shifted and enhanced fluorescence emission, and characteristic 11B NMR shifts. Neutral analogues (Δ9-THC, CBD) do not undergo complexation and therefore lack these features. The integrated voltammetric, fluorometric, and NMR data elucidate the molecular basis of borate-induced selectivity and provide a mechanistic foundation for the rational design of electrochemical sensors for forensic and regulatory applications.