Pitfalls in the analysis of phytocannabinoids in cannabis inflorescence

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Pitfalls in the analysis of phytocannabinoids in cannabis inflorescence Cinzia Citti 1,2,3 & Fabiana Russo 3 & Salvatore Sgrò 4 & Alfonso Gallo 5 & Antonio Zanotto 6 & Flavio Forni 3 & Maria Angela Vandelli 3 & Aldo Laganà 2,7 & Carmela Maria Montone 7 & Giuseppe Gigli 2 & Giuseppe Cannazza 2,3 Received: 23 December 2019 / Revised: 19 February 2020 / Accepted: 26 February 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract The chemical analysis of cannabis potency involves the qualitative and quantitative determination of the main phytocannabinoids: Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), cannabigerol (CBG), cannabichromene (CBC), etc. Although it might appear as a trivial analysis, it is rather a tricky task. Phytocannabinoids are present mostly as carboxylated species at the aromatic ring of the resorcinyl moiety. Their decarboxylation caused by heat leads to a greater analytical variability due to both reaction kinetics and possible decomposition. Moreover, the instability of cannabinoids and the variability in the sample preparation, extraction, and analysis, as well as the presence of isomeric forms of cannabinoids, complicates the scenario. A critical evaluation of the different analytical methods proposed in the literature points out that each of them has inherent limitations. The present review outlines all the possible pitfalls that can be encountered during the analysis of these compounds and aims to be a valuable help for the analytical chemist. Keywords Cannabinoid extraction . Cannabinoid analysis . GC-FID . LC-UV . Mass spectrometry . Cannabis flos monograph

Introduction Cannabis is a chemically complex natural mixture of biologically active compounds spanning flavonoids, amino acids,

* Giuseppe Cannazza [email protected] 1

Mediteknology s.r.l. (CNR spin-off company), Via Arnesano, 73100 Lecce, Italy

2

CNR NANOTEC, Institute of Nanotechnology, Via Monteroni, 73100 Lecce, Italy

3

Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103, 41125 Modena, Italy

4

Chemical Laboratory of Bologna, Anti-Fraud Office - Laboratories Section, Interregional Directorate for Emilia Romagna and Marche, Italian Customs and Monopolies Agency, V.le P.Pietramellara 1/2, 40121 Bologna, Italy

5

Department of Chemistry, Istituto Zooprofilattico Sperimentale del Mezzogiorno, Via Salute 2, 80055 Portici, Italy

6

Canapar s.r.l., Zona Ind.le IV Fase C.da Piancatella, 97100 Ragusa, Italy

7

Department of Chemistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy

sugars, phytocannabinoids, and so forth [1–3]. Among these, phytocannabinoids represent the most interesting and most thoroughly studied class of compounds as they are endowed of a wide range of pharmacological activities. In particular, (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC) and (−)-transcannabidiol (CBD) are the best known phytocannabinoids (Fig. 1), with the former characterized by the intoxicant psychotropic activity typical of cannabis [4–6], a