Discrimination of CBD-, THC- and CBC-type acid cannabinoids through diagnostic ions by UHPLC-HR-MS/MS in negative ion mode.

The interest in industrial hemp-based products and by-products to be utilized in food and nutraceutical sector is strictly linked to the demand for improved analytical methods to rapidly discriminate acid phytocannabinoid isomers. Indeed, the differentiation of acid phytocannabinoids, also named pre-cannabinoids, is not properly exploited and valued until now, and it is challenging. Herein, using high-resolution MS/MS, the most common pre-cannabinoids with the resorcinol core linked to the alkyl five carbons chain were deeply investigated in terms of their reactivity to collision-induced dissociation, gaining key data on the integrated energy framework of their dissociation pathway. In fact, CBD-, THC- and CBC-type pre-cannabinoids could be discriminated based on the base peak identity, and the intensity of common fragment ions, when collision energy fragmented precursor ions by 70-75 %. In particular, energy-resolved CID mass spectra highlighted that fragmentation occurs, unrelatedly to alkyl chain length, at phenolic and monoterpenic moieties levels. Accordingly, this tool is effective for further differentiating pre-cannabinoid homologues, from methyl- up to heptyl-homologues, getting new insight in acid cannabinoids heritage of hemp and its products.