Methods for quantification of cannabinoids: a narrative review

Pourseyed Lazarjani et al. Journal of Cannabis Research https://doi.org/10.1186/s42238-020-00040-2 Journal of Cannabis Research (2020) 2:35 REVIEW Open Access Methods for quantification of cannabinoids: a narrative review Masoumeh Pourseyed Lazarjani1, Stephanie Torres1,2, Thom Hooker3, Chris Fowlie3, Owen Young4 and Ali Seyfoddin1* Abstract Background: Around 144 cannabinoids have been identified in cannabis plant, among them tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most prominent ones. Because of the legal restrictions on cannabis in many countries, it is difficult to obtain standards to use in research; nonetheless, it is important to develop a cannabinoid quantification technique with pharmaceutical applications for quality control of future therapeutic cannabinoids. Method: To find relevant articles for this narrative review paper, a combination of keywords such as medicinal cannabis, analytical, quantification and cannabinoids were searched for in PubMed, EMBASE, MEDLINE, Google Scholar and Cochrane Library (Wiley) databases. Results: The most common cannabinoid quantification techniques include gas chromatography (GC) and highperformance liquid chromatography (HPLC). GC is often used in conjunction with mass spectrometry (MS) or flame ionization detection (FID). The major advantage of GC is terpenes quantification however, for evaluating acidic cannabinoids it needs to be derivatised. The main advantage of HPLC is the ability to quantify both acidic and neutral forms of cannabinoids without derivatisation which is often with MS or ultraviolet (UV) detectors. Conclusion: Based on the information presented in this review, the ideal cannabinoid quantification method is HPLC- MS/MS for the cannabinoids. Keywords: Cannabis, Cannabinoids, Analytical, THC, CBD, Quantification Introduction Cannabis sativa L. is an annual herbaceous flowering plant indigenous to eastern Asia (De Backer et al. 2009). The phenotypes of cannabis are highly variable and the plant is accepted to have two subspecies: C. sativa subsp. sativa and C. sativa subsp. indica (Hillig and Mahlberg 2004; Knight et al. 2010). A third subspecies, C. sativa subsp. ruderalis, has been identified; however, it is not broadly recognized (Fischedick et al. 2010a; Hillig and Mahlberg 2004). Cannabis has been used for its therapeutic properties for thousands of years and it was introduced in western medicine in the nineteenth century * Correspondence: 1 Drug Delivery Research Group, School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand Full list of author information is available at the end of the article until its prohibition in the US from mid-1930s (Aizpurua-Olaizola et al. 2014). The medicinal compounds from cannabis are mostly concentrated in the female flowers of this dioecious species (Fischedick et al. 2010a). The so-called resin is the source of a wide variety of terpenoids and cannabinoids (Fischedick et al. 2010a). The therapeutic properties of cannabis are attributed to cannabinoids (Hazekamp et al. 2014). Cannabinoids are found in the resin produced by the trichomes which are widely distributed on both the male and female plants however are most highly concentrated on the female flowers of the cannabis plant (Citti et al. 2018; De Backer et al. 2009). Cannabinoids are terpenophenolic compounds unique to cannabis (Hillig 2004). To date, 144 cannabinoids have been identified (Hazekamp et al. 2014). The two cannabinoids most well known for their therapeutic properties © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Pourseyed Lazarjani et al. Journal of Cannabis Research (2020) 2:35 are tetrahydrocannabinol (THC) and cannabidiol (CBD) (Aizpurua-Olaizola et al. 2016; Hillig 2004). THC and CBD are the neutral homologs of tetrahydrocannabinolic acid (THCA) and cannabidiol acid (CBDA) respectively (Aizpurua-Olaizola et al. 2016). A conventional classification model of cannabinoids is due to their chemical contents dividing them to eleven subclasses including cannabigerol (CBG), tetrahydrocannabinol (THC), cannabidiol (CBD), cannabichromene (CBC), cannabinol (CBN), (−)-Δ8-transtetrahydrocannabinol (Δ8-THC), cannabicyclol (CBL), cannabinodiol (CBND), cannabielsoin (CBE), cannabitriol (CBT) and miscellaneous (Berman et al. 2018) (Fig. 1). Because consumers have limited means to analyse the chemical composition of the cannabis products, consumers may be inadvertently purchasing products with undesired properties given that different cannabinoids produce different effects (Fischedick et al. 2010b). As a result, it is Page 2 of 10 important to implement methods of quality control so that consumers can be certain that what they are consuming will have the desired effects (Dussy et al. 2005; Fischedick et al. 2010a; Fischedick et al. 2010b). As cannabis use becomes progressively accepted, it becomes increasingly important to quantify the cannabinoid profile and content of cannabis preparations to ensure the uniformity and quality of the preparations (Omar et al. 2014). A variety of analytical techniques have been developed for quantification and qualification cannabinoids and other compounds in cannabis plant. Advances in analytical methods have also resulted in detection of various compounds from cannabis extracts in the last decade (eg terpenes). The purpose of this literature review is to explore cannabinoid quantification techniques and subsequently suggest an optimal method for pharmaceutical grade quantification. Fig. 1 The most common cannabinoids and their conversion pathway by decarboxylation because of heat or aging. CBGA can convert to CBDA and THCA by CBDA synthase and THCA synthase, respectively. CBGA: cannabigerolic acid, CBG: cannabigerol, CBDA: cannabidiolic acid, CBD: cannabidiol, THCA: tetrahydrocannabinolic acid, THC: tetrahyrocannabinol, CBN: cannabinol (Fathordoobady et al. 2019) Pourseyed Lazarjani et al. Journal of Cannabis Research (2020) 2:35 Methods To find relevant papers for this narrative review paper many data bases have been reviewed for 8 months. A combination of keywords (...truncated)