Quantitative Determination of Cannabinoids in Cannabis and Cannabis Products Using Ultra‐High‐Performance Supercritical Fluid Chromatography and Diode Array/Mass Spectrometric Detection

Ultra‐high‐performance supercritical fluid chromatography (UHPSFC) is an efficient analytical technique and has not been fully employed for the analysis of cannabis. Here, a novel method was developed for the analysis of 30 cannabis plant extracts and preparations using UHPSFC/PDA‐MS. Nine of the most abundant cannabinoids, viz. CBD, ∆8‐THC, THCV, ∆9‐THC, CBN, CBG, THCA‐A, CBDA, and CBGA, were quantitatively determined (RSDs < 6.9%). Unlike GC methods, no derivatization or decarboxylation was required prior to UHPSFC analysis. The UHPSFC chromatographic separation of cannabinoids displayed an inverse elution order compared to UHPLC. Combining with PDA‐MS, this orthogonality is valuable for discrimination of cannabinoids in complex matrices. The developed method was validated, and the quantification results were compared with a standard UHPLC method. The RSDs of these two methods were within ±13.0%. Finally, chemometric analysis including principal component analysis (PCA) and partial least squares‐discriminant analysis (PLS‐DA) were used to differentiate between cannabis samples.

[1]  Safwat Ahmed,et al.  Minor oxygenated cannabinoids from high potency Cannabis sativa L. , 2015, Phytochemistry.

[2]  M. Carrott,et al.  A preliminary study of the analysis of Cannabis by supercritical fluid chromatography with atmospheric pressure chemical ionisation mass spectroscopic detection. , 1997, Science & justice : journal of the Forensic Science Society.

[3]  Y. Choi,et al.  Metabolic fingerprinting of Cannabis sativa L., cannabinoids and terpenoids for chemotaxonomic and drug standardization purposes. , 2010, Phytochemistry.

[4]  A. Caligiani,et al.  GC‐MS Analysis of Hashish Samples: A Case of Adulteration with Colophony , 2006, Journal of forensic sciences.

[5]  M. Elsohly,et al.  Cannabinoids in glaucoma II: the effect of different cannabinoids on intraocular pressure of the rabbit. , 1984, Current eye research.

[6]  Ethan B. Russo Cannabis for migraine treatment: the once and future prescription? An historical and scientific review , 1998, Pain.

[7]  Alan B. Jones,et al.  Analysis of the Major Metabolite of Δ9-Tetrahydrocannabinol in Urine II. A HPLC Procedure , 1983 .

[8]  I. Khan,et al.  Biologically active cannabinoids from high-potency Cannabis sativa. , 2009, Journal of natural products.

[9]  H. Göbel [Cannabis in medicine]]. , 2004, Schmerz.

[10]  A. Lichtman,et al.  The psychoactive plant cannabinoid, Δ9‐tetrahydrocannabinol, is antagonized by Δ8‐ and Δ9‐tetrahydrocannabivarin in mice in vivo , 2007, British journal of pharmacology.

[11]  G. Tassoni,et al.  Determination of primary active constituents in Cannabis preparations by high-resolution gas chromatography/flame ionization detection and high-performance liquid chromatography/UV detection , 2002 .

[12]  W. Weinmann,et al.  Simultaneous quantification of delta-9-THC, THC-acid A, CBN and CBD in seized drugs using HPLC-DAD. , 2014, Forensic science international.

[13]  Eric P. Baron,et al.  Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It's Been … , 2015, Headache.

[14]  Raphael Mechoulam,et al.  Cannabidiol: An Overview of Some Pharmacological Aspects , 2002, Journal of clinical pharmacology.

[15]  I. Khan,et al.  Structure determination and absolute configuration of cannabichromanone derivatives from high potency Cannabis sativa. , 2008, Tetrahedron letters.

[16]  I. Khan,et al.  Cannabisol, a novel Δ9-THC dimer possessing a unique methylene bridge, isolated from Cannabis sativa. , 2012, Tetrahedron letters.

[17]  Ruri Kikura-Hanajiri,et al.  A Reliable Method for the Separation and Detection of Synthetic Cannabinoids by Supercritical Fluid Chromatography with Mass Spectrometry, and Its Application to Plant Products. , 2015, Chemical & pharmaceutical bulletin.

[18]  I. Khan,et al.  Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. , 2010, Pharmacology Biochemistry and Behavior.

[19]  Safwat Ahmed,et al.  Cannabinoid ester constituents from high-potency Cannabis sativa. , 2008, Journal of natural products.

[20]  I. Khan,et al.  Microbial metabolism of cannflavin A and B isolated from Cannabis sativa. , 2010, Phytochemistry.

[21]  Maitane Olivares,et al.  Identification and quantification of cannabinoids in Cannabis sativa L. plants by high performance liquid chromatography-mass spectrometry , 2014, Analytical and Bioanalytical Chemistry.

[22]  Lisa Wilson,et al.  Isolation and Pharmacological Evaluation of Minor Cannabinoids from High-Potency Cannabis sativa. , 2015, Journal of natural products.

[23]  Ronald Eugene Shaffer,et al.  Multi‐ and Megavariate Data Analysis. Principles and Applications, I. Eriksson, E. Johansson, N. Kettaneh‐Wold and S. Wold, Umetrics Academy, Umeå, 2001, ISBN 91‐973730‐1‐X, 533pp. , 2002 .

[24]  A. Zuardi History of cannabis as a medicine: a review. , 2006, Revista brasileira de psiquiatria.

[25]  G. Golding,et al.  Quantitative GC-MS analysis of D(9)-tetrahydrocannabinol in fiber hemp varieties. , 2005, Journal of analytical toxicology.

[26]  Safwat Ahmed,et al.  Isolation and characterization of new Cannabis constituents from a high potency variety. , 2008, Planta medica.

[27]  R. Marsili,et al.  Hair testing for delta9-THC-COOH by gas chromatography/tandem mass spectrometry in negative chemical ionization mode. , 2005, Rapid communications in mass spectrometry : RCM.

[28]  W. Maule,et al.  Suppression of the cardiac conditioned response by Δ-9-tetrahydrocannabinol: A comparison with other drugs , 1976, Psychopharmacology.

[29]  J. Cocho,et al.  An improved method for the determination of ∆9-tetrahydrocannabinol, cannabinol and cannabidiol in hair by liquid chromatography–tandem mass spectrometry , 2014 .

[30]  Maitane Olivares,et al.  Optimisation and characterisation of marihuana extracts obtained by supercritical fluid extraction and focused ultrasound extraction and retention time locking GC-MS. , 2013, Journal of separation science.

[31]  M. Salem,et al.  Chapter 5 Cannabinoids analysis: analytical methods for different biological specimens , 2008 .

[32]  J. Drewe,et al.  Development of a LC/MS/MS method for the analysis of cannabinoids in human EDTA-plasma and urine after small doses of Cannabis sativa extracts. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[33]  Benjamin Debrus,et al.  Innovative development and validation of an HPLC/DAD method for the qualitative and quantitative determination of major cannabinoids in cannabis plant material. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[34]  J. Amigo,et al.  Resolution of co-eluting compounds of Cannabis Sativa in comprehensive two-dimensional gas chromatography/mass spectrometry detection with Multivariate Curve Resolution-Alternating Least Squares. , 2014, Talanta.

[35]  W. Rowe,et al.  Assessment of ultra high performance supercritical fluid chromatography as a separation technique for the analysis of seized drugs: Applicability to synthetic cannabinoids. , 2016, Journal of chromatography. A.

[36]  Thomas A. Briellmann,et al.  Isolation of Δ9-THCA-A from hemp and analytical aspects concerning the determination of Δ9-THC in cannabis products , 2005 .

[37]  I. Khan,et al.  Non-cannabinoid constituents from a high potency Cannabis sativa variety. , 2008, Phytochemistry.

[38]  B. Porter,et al.  Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy , 2013, Epilepsy & Behavior.

[39]  V. Henn,et al.  Delta-9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double-blind trial , 2005, European Archives of Psychiatry and Clinical Neuroscience.

[40]  I. Nathan,et al.  Cannabinoids block release of serotonin from platelets induced by plasma from migraine patients. , 1985, International journal of clinical pharmacology research.

[41]  Natalia Pinho de Oliveira Ribeiro,et al.  Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug. , 2012, Revista brasileira de psiquiatria.

[42]  D. Later,et al.  Analysis of various classes of drugs by capillary supercritical fluid chromatography. , 1986, Journal of chromatographic science.

[43]  Julian Broséus,et al.  The differentiation of fibre- and drug type Cannabis seedlings by gas chromatography/mass spectrometry and chemometric tools. , 2010, Forensic science international.

[44]  R L Sperling,et al.  "What a long, strange trip it's been". , 2000, Home healthcare nurse.

[45]  R Zimmermann,et al.  Application of two-dimensional gas chromatography combined with pixel-based chemometric processing for the chemical profiling of illicit drug samples. , 2008, Journal of chromatography. A.