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Analytical chemists from Stellenbosch University (SU) have provided the first evidence of a rare class of phenolics, called flavoalkaloids, in cannabis leaves.

Phenolic compounds, especially flavonoids, are well-known and sought after in the pharmaceutical industry because of their antioxidant, anti-inflammatory, and anti-carcinogenic properties.

The researchers identified 79 phenolic compounds in three strains of cannabis grown commercially in South Africa, of which 25 were reported for the first time in cannabis. Sixteen of these compounds were tentatively identified as flavoalkaloids. Interestingly, the flavoalkaloids were mainly found in the leaves of only one of the strains. The results were published in the recently.

Dr. Magriet Muller, an analytical chemist in the LC-MS laboratory of the Central Analytical Facility (CAF) at Stellenbosch University and first author on the paper, says the analysis of plant phenolics is challenging due to their low concentration and extreme structural diversity.

"Most plants contain highly complex mixtures of phenolic compounds, and while flavonoids occur widely in the plant kingdom, the flavoalkaloids are very rare in nature," she explains.

"We know that cannabis is extremely complex—it contains more than 750 metabolites—but we did not expect such high variation in phenolic profiles between only three strains, nor to detect so many compounds for the first time in the species. In particular, the first evidence of flavoalkaloids in cannabis was very exciting."

For her postgraduate studies in SU's Department of Chemistry and Polymer Science, she developed powerful analytical methods combining comprehensive two-dimensional liquid chromatography and high-resolution mass spectrometry for the detailed characterization of phenolic compounds.

"We were looking for a new application for the methods that I developed, after successfully testing them on rooibos tea, grapes and wine. I then decided to apply the methods to cannabis because I knew it was a complex sample, and that cannabis phenolics have not been well characterized," she explains.

According to Prof. André de Villiers, her study leader and main author on the paper, he was blown away by the chromatographic results that Muller obtained: "The excellent performance of two-dimensional liquid chromatography allowed separation of the flavoalkaloids from the much more abundant flavonoids, which is why we were able to detect these rare compounds for the first time in cannabis." He leads the analytical chemistry research group in SU's Department of Chemistry and Polymer Science.

Prof. De Villiers says it is obvious there is still much to gain from studying cannabis, as the bulk of research in this field to date has been focused on the pharmacological properties of the mood-effecting cannabinoids.

"Our analysis again highlights the medicinal potential of cannabis plant material, currently regarded as waste. Cannabis exhibits a rich and unique non-cannabinoid phenolic profile, which could be relevant from a biomedical research perspective," he concludes.