Download PDF
Planta Med 2020; 86(05): 338-347
DOI: 10.1055/a-1110-1045
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

GC-MS Metabolite Profile and Identification of Unusual Homologous Cannabinoids in High Potency Cannabis sativa

Josep Basas-Jaumandreu
Department of Mining, Industrial and ICT, Escola Politècnica Superior dʼEnginyeria de Manresa (EPSEM), Universitat Politècnica de Catalunya (UPC-BarcelonaTech), Manresa, Catalonia, Spain
,
F. Xavier C. de las Heras
Department of Mining, Industrial and ICT, Escola Politècnica Superior dʼEnginyeria de Manresa (EPSEM), Universitat Politècnica de Catalunya (UPC-BarcelonaTech), Manresa, Catalonia, Spain
› Author Affiliations
Further Information

Publication History

received 14 August 2019
revised 30 December 2019

accepted 26 January 2020

Publication Date:
13 February 2020 (online)

Also available at
    Permissions and Reprints

Abstract

Phytochemical investigation of the lipids extracted from seeds of Cannabis sativa by GC-MS showed 43 cannabinoids, 16 of which are new. The extract is dominated by Δ9-tetrahydrocannabinolic acid (A) and its neutral derivative trans-Δ9-tetrahydrocannabinol-C5 (THC) Cis and trans-Δ9-tetrahydrocannabinol-C7 isomers with an ethyl-pentyl branched chain together with minor amounts of trans-Δ9-tetrahydrocannabinol with a methyl-pentyl C6 branched side chain were identified as new natural compounds. Four cannabichromene isomers with a C5 side chain are postulated to be derived from the double bond migration at the terminal isoprenyl unit. C7 cannabichromene together with the neutral and acidic forms of cannabinol-C7 were also detected. The mass spectrum of these homologues as trimethylsilyl (TMS) derivatives are presented, and the fragmentation patterns are discussed.

Key words

Cannabinoids - Cannabis sativa - Cannabaceae - phytochemical analysis - GC-MS

Supporting Information

 

  • References

  • 1 Clarke RC, Watson DP. Cannabis and natural Cannabis Medicines. In: El-Sohly MA. ed. Marijuana and the Cannabinoids. Totowa, New Jersey: Humana Press Inc; 2007: 1-16
    CrossrefSearch in Google Scholar
  • 2 Mechoulam R. Cannabinoids as Therapeutics. Basel: Virkhäuser; 2005: 1-264
    CrossrefSearch in Google Scholar
  • 3 Radwan MM, Wanas AS, Chandra S, El-Sohly MA. Natural Cannabinoids of Cannabis and Methods of Analysis. In: Chandra S, Lata H, El-Sohly MA. eds. Cannabis sativa L. – Botany and Biotechnology. Cham, Switzerland: Springer International Publishing AG; 2017: 161-182
    Search in Google Scholar
  • 4 United Nation Office on Drugs and Crime (UNODC). Cannabis: a short review. Published 2012. Available at: https://www.unodc.org/documents/drug-prevention-and-treatment/cannabis_review.pdf Accessed September 28, 2019
    PubMed
  • 5 El-Sohly MA, Radwan MM, Gul W, Chandra S, Galal A. Phytochemistry of Cannabis sativa L. In: Kinghorn A, Falk H, Gibbons S, Kobayashi J. eds. Phytocannabinoids. Progress in the Chemistry of organic natural Products, Volume 103. Cham, Switzerland: Springer International Publishing AG; 2017: 1-36
    Search in Google Scholar
  • 6 Shoyama Y, Yagi M, Nishioka I, Yamautchi T. Biosynthesis of cannabinoid acids. Phytochemistry 1975; 14: 2189-2192
    CrossrefPubMedSearch in Google Scholar
  • 7 Veress T, Szanto JI, Leisztner L. Determination of cannabinoid acids by high-performance liquid chromatography of their neutral derivatives formed by thermal decarboxylation. J Chromatogr A 1990; 520: 339-347
    CrossrefPubMedSearch in Google Scholar
  • 8 Razdan RK. Structure-activity relationships in cannabinoids. Pharmacol Rev 1986; 38: 75-149
    PubMedSearch in Google Scholar
  • 9 Fetterman PS, Keith ES, Waller CW, Guerrero O, Doorenbos NJ, Quimby MW. Mississippi-grown Cannabis sativa L.: Preliminary observation on chemical definition of phenotype and variations in tetrahydrocannabinol content versus age, sex, and plant part. J of Pharm Sci 1971; 60: 1246-1249
    CrossrefPubMedSearch in Google Scholar
  • 10 Billets S, El-Feraly F, Fetterman PS, Turner CE. Constituents of Cannabis sativa L. XII-Mass spectral fragmentation patterns for some cannabinoid acids as their TMS derivatives. Org Mass Spectrom 1976; 11: 741-751
    CrossrefPubMedSearch in Google Scholar
  • 11 Hanus LO. Pharmacological and therapeutic secrets of plant and brain (endo)cannabinoids. Med Res Rev 2009; 29: 213-271
    CrossrefPubMedSearch in Google Scholar
  • 12 Harvey DJ. Mass spectrometry of the cannabinoids and their metabolites. Mass Spectrom Rev 1987; 6: 135-229
    CrossrefPubMedSearch in Google Scholar
  • 13 Moore M, Rickards RW, Ronneberg H. Cannabinoid studies. IV. Stereoselective and regiospecific syntheses of (±)-Δ9-trans- and (±)-Δ9-cis-6a,10a-tetrahydrocannabinol. Aust J Chem 1984; 37: 2339-2348
    CrossrefPubMedSearch in Google Scholar
  • 14 Lewis R, Ward S, Johnson R, Thorburn Burns D. Distribution of the principal cannabinoids within bars of compressed cannabis resin. Anal Chim Acta 2005; 538: 399-405
    CrossrefPubMedSearch in Google Scholar
  • 15 Gaoni Y, Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc 1964; 86: 1646-1647
    CrossrefPubMedSearch in Google Scholar
  • 16 Harvey DJ. The mass spectra of the trimethylsilyl derivatives of Δ1- and Δ6-tetrahydrocannabinol. Biomed Mass Spectrom 1981; 8: 575-578
    CrossrefPubMedSearch in Google Scholar
  • 17 Vree TB. Mass spectrometry of cannabinoids. J Pharm Sci 1977; 66: 1444-1450
    CrossrefPubMedSearch in Google Scholar
  • 18 Choi YH, Hazekamp A, Peltenburg-Looman AMG, Frédérich M, Erkelens C, Lefeber AWM, Verpoorte R. NMR assignments of the major cannabinoids and cannabiflavonoids isolated from flowers of Cannabis sativa . Phytochem Anal 2004; 15: 345-354
    CrossrefPubMedSearch in Google Scholar
  • 19 Brown NK, Harvey DJ. Metabolism of n-hexyl-homologues of delta-8-tetrahydrocannabinol and delta-9-tetrahydrocannabinol in the mouse. Eur J Drug Metab Ph 1988; 13: 165-176
    CrossrefPubMedSearch in Google Scholar
  • 20 Goad LJ, Hammam ASA, Dennis A, Goodwin TW. Biosynthesis of the phytosterol side chain. Nature 1966; 210: 1322-1324
    CrossrefPubMedSearch in Google Scholar
  • 21 Nes WD, Song Z, Dennis AL, Zhou W, Nam J, Miller MB. Biosynthesis of phytosterols kinetic mechanism for the enzymatic C-methylation of sterols. J Biol Chem 2003; 278: 34505-34516
    CrossrefPubMedSearch in Google Scholar
  • 22 Groeneveld HW. Tracing steroid synthesis in plants. Crit Rev Biochem Mol 1999; 34: 59-69
    CrossrefPubMedSearch in Google Scholar
  • 23 Harvey DJ. Cyclic alkylboronates as derivatives for the characterization of cannabinolic acids by combined gas chromatography and mass spectrometry. Biomed Mass Spectrom 1977; 4: 88-93
    CrossrefPubMedSearch in Google Scholar
  • 24 Harvey DJ. Stability of cannabinoids in dried samples of cannabis dating from around 1896–1905. J Ethnopharmacol 1990; 28: 117-128
    CrossrefPubMedSearch in Google Scholar
  • 25 Harvey DJ, Brown NK. Electron impact-induced fragmentation of the trimethylsilyl derivatives of monohydroxy-hexahydrocannabinols. Biol Mass Spectrom 1991; 20: 292-302
    CrossrefPubMedSearch in Google Scholar
  • 26 Turner CE, El-Sohly MA. Biological activity of cannabichromene, its homologs and isomers. J Clin Pharmacol 1981; 21: 283-291
    CrossrefPubMedSearch in Google Scholar
  • 27 Ross SA, El-Sohly MA, Sultana GNN, Mehmedic Z, Hossain ChF, Chandra S. Flavonoid glycosides and cannabinoids from the pollen of Cannabis sativa L. Phytochem Anal 2005; 16: 45-48
    CrossrefPubMedSearch in Google Scholar
  • 28 Hazekamp A, Peltenburg A, Verpoorte R, Giroud C. Chromatographic and spectroscopic data of cannabinoids from Cannabis sativa L. J. Liq Chromatogr Relat Technol 2005; 28: 2361-2382
    PubMedSearch in Google Scholar
  • 29 El-Sohly MA, Slade D. Chemical constituents of marijuana: The complex mixture of natural cannabinoids. Life Sci 2005; 78: 539-548
    CrossrefPubMedSearch in Google Scholar
  • 30 Adams RP. Identification of essential Oil Components by Gas Chromatography/Mass Spectrometry, 4th edition. Illinois: Allured Publishing Corporation; 2007
    Search in Google Scholar
  • 31 Degenhardt F, Stehle F, Kayser O. The Biosynthesis of Cannabinoids. In: Preedy V. ed. Handbook of Cannabis and related Pathologies. London: Elsevier; 2017: 13-23
    CrossrefSearch in Google Scholar
  • 32 Mechoulam R, Yagen B. Stereoselective cyclization of cannabinoid 1,5 diene. Tetrahedron Lett 1969; 60: 5349-5352
    PubMedSearch in Google Scholar
  • 33 Hanus LO, Levy R, De La Vega D, Katz L, Roman M, Tomícek P. The main cannabinoids content in hashish samples seized in Israel and Czech Republic. Israel J. Plant Sci 2016; 63: 182-190
    PubMedSearch in Google Scholar
  • 34 Harvey DJ, Brown NK. A method for the structural determination of cannabichromene metabolites by mass spectrometry. Rapid Commun Mass Sp 1990; 4: 135-136
    CrossrefPubMedSearch in Google Scholar
  • 35 Taura F, Morimoto S, Shoyama Y. Cannabinerolic acid, a cannabinoid from Cannabis sativa . Phytochemistry 1995; 39: 457-458
    CrossrefPubMedSearch in Google Scholar
  • 36 Fellermeier M, Zenk MH. Prenylation of olivetolate by a hemp transferase yields cannabigerolic acid, the precursor of tetrahydrocannabinol. FEBS Lett 1998; 427: 283-285
    CrossrefPubMedSearch in Google Scholar
  • 37 Gaoni Y, Mechoulam R. The structure and synthesis of cannabigerol, a new hashish constituent. Proc Chem Soc 1964; 82
    PubMedSearch in Google Scholar
  • 38 Radwan M, Ross S, Slade D, Ahmed S, Zulfiqar F, El-Sohly M. Isolation and characterization of new cannabis constituents from a high potency variety. Planta Med 2008; 74: 267-272
    Thieme ConnectPubMedSearch in Google Scholar
  • 39 Cardenia V, Toschi TG, Scappini S, Rubino RC, Rodriguez-Estrada MT. Development and validation of a fast gas chromatography/mass spectrometry method for the determination of cannabinoids in Cannabis sativa L. J Food Drug Anal 2018; 4: 1283-1292
    PubMedSearch in Google Scholar
  • 40 Budzikiewicz H, Alpin RT, Lightner DA, Djerassi C, Mechoulam R, Gaoni Y. Massenspektroskopie und ihre Anwendung auf strukturelle und stereochemische Probleme-LXVIII. Massenspektroskopische Untersuchung der Inhaltstoffe von Haschisch. Tetrahedron 1965; 21: 1881-1888
    CrossrefPubMedSearch in Google Scholar
  • 41 Kinzer GW, Foltz RL, Mitchell RI, Battelle. Truitt EB. The fate of the cannabinoid components of marihuana during smoking. Bull Narcot 1974; 26: 41-54
    PubMedSearch in Google Scholar
  • 42 El-Sohly MA, El-Feraly FS, Turner CE. Isolation and characterization of (+)-cannabitriol and (−)-10-ethoxy-9-hydroxy-Δ6a(10a)-tetrahydrocannabinol: two new cannabinoids from Cannabis sativa L. extract. Lloydia 1977; 40: 275-280
    PubMedSearch in Google Scholar
  • 43 Roth N, Wohlfarth A, Auwärter V. Regioselective synthesis of THCA-A and THCA-B by reaction of Δ9-THC with magnesium methyl carbonate (MMC). Toxichem Krimtech 2011; 78: 316-319
    PubMedSearch in Google Scholar
  • 44 Harvey DJ, Brown NK. Identification of cannabichromene metabolites by mass spectrometry: identification of eight new dihydroxy metabolites in the rabbit. Biol Mass Spectrom 1991; 20: 275-285
    CrossrefPubMedSearch in Google Scholar
  • 45 Lee YR, Xia L. Efficient one-pot synthetic approaches for cannabinoid analogues and their application to biologically interesting (−)-hexahydrocannabinol and (+)-hexahydrocannabinol. Tetrahedron Lett 2008; 49: 3283-3287
    CrossrefPubMedSearch in Google Scholar