Constituents of Cannabis sativa L. VII: Use of Silyl Derivatives in Routine Analysis

Turner, Carlton E.; Hadley, Kathy W.; Henry, Janis; Mole, M. Leonard

doi:10.1002/jps.2600631209

Cited by 43 publications

(16 citation statements)

References 12 publications

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“…Hypothetically these products contain THCA-B, which crystalizes more readily than THCA-A. 2 THCA-B also demonstrates greater thermal stability than THCA-A, 32–34 so it may be worth investigating. However, only two studies have quantified THCA-A and THCA-B content in a variety of Cannabis landraces, 33,34 so the prevalence of THCA-B is relatively unknown.…”

Section: Discussionmentioning

confidence: 99%

Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two

McPartland

Macdonald

Young

et al. 2017

Cannabis and Cannabinoid Research

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Introduction: Cannabis biosynthesizes Δ9-tetrahydrocannabinolic acid (THCA-A), which decarboxylates into Δ9-tetrahydrocannabinol (THC). There is growing interest in the therapeutic use of THCA-A, but its clinical application may be hampered by instability. THCA-A lacks cannabimimetic effects; we hypothesize that it has little binding affinity at cannabinoid receptor 1 (CB1).Materials and Methods: Purity of certified reference standards were tested with high performance liquid chromatography (HPLC). Binding affinity of THCA-A and THC at human (h) CB1 and hCB2 was measured in competition binding assays, using transfected HEK cells and [3H]CP55,940. Efficacy at hCB1 and hCB2 was measured in a cyclic adenosine monophosphase (cAMP) assay, using a Bioluminescence Resonance Energy Transfer (BRET) biosensor.Results: The THCA-A reagent contained 2% THC. THCA-A displayed small but measurable binding at both hCB1 and hCB2, equating to approximate Ki values of 3.1μM and 12.5μM, respectively. THC showed 62-fold greater affinity at hCB1 and 125-fold greater affinity at hCB2. In efficacy tests, THCA-A (10μM) slightly inhibited forskolin-stimulated cAMP at hCB1, suggestive of weak agonist activity, and no measurable efficacy at hCB2.Discussion: The presence of THC in our THCA-A certified standard agrees with decarboxylation kinetics (literature reviewed herein), which indicate contamination with THC is nearly unavoidable. THCA-A binding at 10μM approximated THC binding at 200nM. We therefore suspect some of our THCA-A binding curve was artifact—from its inevitable decarboxylation into THC—and the binding affinity of THCA-A is even weaker than our estimated values. We conclude that THCA-A has little affinity or efficacy at CB1 or CB2.

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Section: Discussionmentioning

confidence: 99%

Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two

McPartland

Macdonald

Young

et al. 2017

Cannabis and Cannabinoid Research

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“…3,4) Only four of the 66 known natural cannabinoids 5) are currently commercially available as certified reference standards, i.e. : (Ϫ)-delta-9-tetrahydrocannabinol (D 9 -THC or THC), (Ϫ)-delta-8-tetrahydrocannabinol (D 8 -THC), cannabidiol (CBD) and cannabinol (CBN). There are indications that also these reference compounds have to be re-quantified regularly because of degradation and differences between batches during production.…”

Section: )mentioning

confidence: 99%

“…7) For the quantitative analysis of these compounds, GC with FID or other detection has been widely used, but this method can not distinguish between cannabinoids and their carboxylic counterparts without prior derivatization. 8,9) HPLC with UV detection is more suitable for simultaneous analysis of these compounds, but it proves to be very difficult to separate all components in a single chromatographic run 10,11) and some contaminations cannot be detected because they lack UV absorbance. Furthermore, both methods are sensitive to impurities in the sample, e.g.…”

Section: )mentioning

confidence: 99%

Quantitative Analysis of Cannabinoids from Cannabis sativa Using 1H-NMR

2004

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The cannabis plant has been of medicinal interest for centuries. In recent years a lot of research on the medical applications of Cannabis sativa L. has been initiated, as several, mostly European, countries move towards a more liberal view on the use of Cannabis as a medicine. Many different pharmacological properties have been associated with cannabis use, including increased heart rate, drop of body temperature, ataxia and a loss of time-space perception. 1)Amongst the constituents of Cannabis sativa, the cannabinoids have been recognized as the active constituents for most clinical activities. The cannabinoids make up a large family of closely related C 21 compounds and their carboxylic acids and are unique to the cannabis plant.2) Pharmacological activites of the cannabinoids are very diverse, ranging from analgetic and antiemetic to the treatment of glaucoma and multiple sclerosis.3,4) Only four of the 66 known natural cannabinoids 5) are currently commercially available as certified reference standards, i.e.: (Ϫ)-delta-9-tetrahydrocannabinol (D 9 -THC or THC), (Ϫ)-delta-8-tetrahydrocannabinol (D 8 -THC), cannabidiol (CBD) and cannabinol (CBN). There are indications that also these reference compounds have to be re-quantified regularly because of degradation and differences between batches during production. 5)Recently, our laboratory developed a method for the large scale isolation of highly pure cannabinoids from Cannabis sativa flower tops. 7) For the quantitative analysis of these compounds, GC with FID or other detection has been widely used, but this method can not distinguish between cannabinoids and their carboxylic counterparts without prior derivatization.8,9) HPLC with UV detection is more suitable for simultaneous analysis of these compounds, but it proves to be very difficult to separate all components in a single chromatographic run 10,11) and some contaminations cannot be detected because they lack UV absorbance. Furthermore, both methods are sensitive to impurities in the sample, e.g. chlorophyll or lipids, and they usually require a sample clean-up step prior to analysis. Most importantly, the reference compounds needed for the preparation of a calibration curve are not available for many cannabinoids. A review of methods for cannabinoids analysis in biological materials is given by Raharjo. 12)To solve the problems associated with these analytical techniques, the development of a reliable and easy method is required as alternative to the conventional analyses. In this study, we developed an analytical method using 1 H-NMR for cannabinoids without the need for any chromatographic purification. Quantitative NMR has been shown to be very accurate and highly reproducible, within a very short analysis time. The usefulness of quantitative NMR for the validation of natural product reference compounds as well as theoretical aspects have been shown by Maniara and Pauli. 13,14) The developed method was applied on the quantitative analysis of five different isolated cannabinoids. A similar method ha...

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“…With such methods, however, the direct analysis of cannabinoid acids is not possible because they decompose thermally by decarboxylation [3][4][5][6][7][8]. The detection limit is i ~tg for Ag-tetrahydrocannabinol (Ag-THC).…”

Section: Introductionmentioning

confidence: 99%

Analysis of cannabinoids by liquid chromatography— Thermospray mass spectrometry and liquid chromatography— Tandem mass spectrometry

1998

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Key WordsColumn liquid chromatography-mass spectrometry Thermospray Identification and quantification A9-tetrahydrocannabinolic acid A9-tetrahydrocannabinol Cannabinol Cannabidiol SummaryA rapid method based on liquid chromatography and thermospray mass spectrometry without any derivatization or pre-purification steps has been developed for the identification and quantification of cannabinoids in drugs from cannabis plants. The extracts were separated on a Cl8 reversed-phase column with an acidic acetonitrile-water gradient, Liquid chromatographymass spectrometry was performed with a thermospray interface and protonated molecular ions were obtained from the cannabinoids of interest. Liquid chromatography-tandem mass spectrometry experiments on the molecular ions gave additional structural information online. The sensitivity and selectivity of the method was sufficient to enable the detection of 100 pg of the cannabinoids.

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Constituents of Cannabis sativa L. VII: Use of Silyl Derivatives in Routine Analysis

Cited by 43 publications

References 12 publications

Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two

Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two

Quantitative Analysis of Cannabinoids from Cannabis sativa Using 1H-NMR

Analysis of cannabinoids by liquid chromatography— Thermospray mass spectrometry and liquid chromatography— Tandem mass spectrometry

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