Tetrahydrocannabinol, determination

The chemical structure of A -tetrahydrocannabinol, determined by Gaoni and Mechoulam in 1964, is illustrated in Figure 6.3. Unlike many other biologically active chemicals of plant origin, A -tetrahydrocannabinol is a highly hydrophobic molecule, a property that has hindered the progress on its mode of action for nearly three decades. Indeed, not only was A -tetrahydrocannabinol more difficult to handle experimentally than such hydrophylic alkaloids as cocaine or morphine, but also its preference for lipid... 

M. Kala, M. Kochanowski. The Determination of A9-Tetrahydrocannabinol (9THC) and 11-nor-9-Carboxy-A9-Tetrahydrocannabinol (THCCOOH) in Blood and Urine Using Gas Chromatography Negative Ion Chemical Ionisation Mass Spectrometry (GC-MS-NCI), Chemical Analysis (Warsaw), 51, 2006. 

Breindahl T, Andreasen K. 1999. Determination of 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid in urine using high-performance liquid chromatography and electrospray ionization mass spectrometry. J Chromatogr B Biomed Sci Appl 732 155. 

Maralikova B, Weinmann W. 2004 Simultaneous determination of Delta9-tetrahydrocannabinol, ll-hydroxy-Delta9-tetrahydrocannabinol and ll-nor-9-carboxy-Delta9-tetra-hydrocannnabinol in human plasma by high-performance liquid chromatography/tandem mass spectrometry. J Mass Spectrom 39 526. 

Tai SS, Welch MJ. 2000. Determination of ll-nor-delta9-tetrahydrocannabinol-9-carboxylic acid in a urine-based standard reference material by isotope-dilution liquid chromatography-mass spectrometry with electrospray ionization. J Anal Toxicol 24 385. 

Kanter, S. L., M. R. Musumeci and L. E. Hollister. Quantitative determination of delta9-tetrahydrocannabinol and delta9-tetrahydrocannabinolic acid in marihuana by high-pressure liquid chromatography. J Chromatogr 1979 171 504. 

V. Kircher and H. Parlar, Determination of A9 tetrahydrocannabinol from human saliva by tandem immunoaffinity chromatography-high-performance liquid chromatography , J. Chromatogr. B 677 245 - 255 (1996). 

The determination (3) of physical and chemical properties such as solubility, stability, pKa, glassbinding and protein-binding of A -tetrahydrocannabinol 1 and correlated congeners were only possible after the development of new high pressure liquid chromatography (HPLC) techniques and the modification of gas liquid chromatography (GLC) technologies. 

Clinical investigations of A -tetrahydrocannabinol (4,5) and ll-hydroxy-A -tetrahydrocannabinol (6) have relied upon analysis by radioactive labeling. However, the study of distribution, metabolism and excretion of the drug and its metabolites under chronic or "street" conditions demands nonradioactive analytical procedures. When plasma suspensions of l c-A -tetrahydrocan-nabinol were administered intravenously to three dogs at doses of 0.1 - 2.0 mg/kg and plasma levels of 1 were followed for up to 7000 minutes, no significant differences were seen in 1 plasma levels as determined by liquid scintillation and electron capture detection (GLC) after HPLC collection. 

The solubilities of A9-tetrahydrocannabinol were determined (7) by two methods 1) Beer s law plots were obtained by plotting the absorbance at one wavelength (225 nm) versus the amount of tetrahydrocannabinol added. The solubility of tetrahydrocannabinol was determined as that concentration at which deviation from Beer s law was observed 2) A modification of the procedure of Saad and Higuchi (11) for determining solubility by using a particle-size counter was also used ... 

A8 -tetrahydrocannabinol were quantitatively separated with respective retention volumes of 6.37 and 6.62 ml (the dead volume between the UV detector and the collection point was 0.46 ml as determined by the iodoform test). Cannabidiol in the same system had a retention volume of 6.06 ml. 

Another MEKC separation (75 mM SDS, phosphate-borate buffer, pH 9.1) was reported for die determination of ll-nor-A-9-tetrahydrocannabinol-9-carboxylic acid, the major metabolite of A-9-tetrahydrocannabinol present in urine (Wemly and Thormann, 1992a). Sample treatment included basic hydrolysis of urine (5 mL), solid phase extraction, and concentration. The resulting sensitivity was 10 to 30 ng/mL (i.e., comparable to the cutoffs of immunoassays). Again, detection was by on-line recording of peak spectra, by means erf fast-scanning UV detector. 

This method can be used to identify the pattern of compounds typical of cannabis. It can also be used to determine whether or not cannabinol is present in the sample. Cannabinol is the breakdown product of -tetrahydrocannabinol. If this is present, the sample is understood to have started to decompose and it should not be used for comparative purposes. It is for this reason that analysis for comparative purposes is not generally carried out more than three months after sample seizure. 

There are a number of reasons why derivatization of samples is necessary. First, the hydroxide and carboxylic moieties may form hydrogen-bonds in the gas phase, thus resulting in poor chromatography. Secondly, the compounds may sorb onto the chromatographic system, resulting in poor chromatography performance, peak shape, and in the case of very low concentrations, non-detection of the analytes. Furthermore, it is known that -tetrahydrocannabinol carboxylic acid thermally decarboxylates at temperatures above 110-120° C, and converts into A -tetrahydrocannabinol. While in some laboratories this is assumed to be quantitative, this may not always be the case. Derivatization will allow determination of both the A -tetrahydrocannabinol and its carboxylic acid. In addition, in the case of very low concentrations of analytes, derivatization will improve the limits of determination and quantification. 

Stanaszek, R., Zuba, D. A comparison of developed and validated chromatographic methods (FIPLC, GC MS) for determination of delta-9-tetrahydrocannabinol (5 -TFIC) and delta-9-tetrahydrocannabinolic acid (5 -TFICA-A) in hemp. Probl. Forensic Sci. 71, 313-322 (2007)... 

Several investigations have been carried out over the years to isolate THC from the plant material, mostly to determine its chemical structure or to investigate the phytochemistry of the plant. In 1942, Wollner, et al., (11) reported the isolation of tetrahydrocannabinol from cannabis extract red oil . Red oil was prepared by extraction of the plant material with ether, followed by distillation of the concentrated extract at room pressure followed by redistillation under reduced pressure (15-50 mm Hg). 

Two new propyl-side-chain cannabinoids are propyl homologues of cannabi-chromene and cannabigerol. Butyl homologues of A -THC, cannabinol, can-nabidiol, and A -tetrahydrocannabinolic acid have been detected. The structure of cannabispiran (257) has been determined by X-ray analysis. By observing the... 

Ross RA, Gibson TM, Stevenson LA, Saha B, Crocker P, Razdan RK, Pertwee RG (1999b) Structural determinants of the partial agonist-inverse agonist properties of 6 -azidohex-2 -yne-A8-tetrahydrocannabinol at cannabinoid receptors. Br J Pharmacol 128 735-743... 

Fig. 3. Plasma zl -tetrahydrocannabinol (THC), H-hydroxy-zl -tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-zl -tetrahydrocannabinol (THCCOOH) concentrations in one participant over 24 h following administration of two 2.5-mgdronabinol(syntheticTHC) doses. Time zero is the time ofthefirst blood draw at 0730 hours. The 2.5-mg doses were administered with food at 1200 and 1800 (4.5 and 10.5 h after time zero). (Reprinted from Journal of Chromatography B, 789, Gustafson et al.. Validated method for the simultaneous determination of delta-9-tetrahydrocannabinol (THC), 1 Thydroxy-THC and 1 Tnor-9-carboxy-THC in human plasma using solid phase extraction and gas chromotography-mass spectrometry with positive chemical ionization, pp. 145, Fig. 2 therein. Copyright (2003) with permission from Elsevier)...

Gustafson RA, Moolchan ET, Barnes A, Levine B, Huestis MA (2003) Validated method for the simultaneous determination of delta-9-tetrahydrocannabinol (THC), 11-hydroxy-THC and 1 l-nor-9-carboxy-THC in human plasma using solid phase extraction and gas chromatography-mass spectrometry with positive chemical ionization. J Chromatogr B Analyt Technol Biomed Life Sci 798 145-154... 

Hanson VW, Buonarati MH, Basel RC, Wade NA, Yep C, Biasotti AA, Reeve VC, Wong AS, OrbanowskyMW (1983) Comparison of3H-and 1251-radioimmunoassay and gas chromatography/mass spectrometry for the determination of delta-9-tetrahydrocannabinol and cannabinoids in blood and serum. J Anal Toxicol 7 96-102... 

Huang W, Moody DE, Andrenyak DM, Smith EK, Foltz RL, Huestis MA, Newton JF (2001) Simultaneous determination of delta-9-tetrahydrocannabinol and ll-nor-9-carboxy-delta-9-tetrahydrocannabinol in human plasma by solid phase extraction and gas chromatography—negative ion chemical ionization—mass spectrometry. J Anal Toxicol 25 531-537... 

Johansson E, Noren K, Sjovall J, Halidin MM (1989b) Determination of delta-1-tetrahydrocannabinol in human fat biopsies from marihuana users by gas chromatography-mass spectrometry. Biomed Chromatogr 3 35-38... 

THC, or tetrahydrocannabinol, is one of many cannabi-nols in marijuana. It is often synthesized in connection with government research projects to clinically determine the reaction of subjects to grass, and is extremely costly to produce. Reactions are almost identical to marijuana use, though more unpredictable because it is a synthetic, and can last 4 to 10 hour s. It s unbelievably expensive to synthesize. 

Few of the recently published reference books covering natural products provide the chemist, within a single volume, with most of the detail which is frequently required, viz. names, structure, physical data, together with references to occurrence, structure determination, and synthesis. The revised edition of Karrer, and its first supplement,do provide this detail in their comprehensive coverage of plant products. This strength makes these volumes indispensable, despite the delay in covering the literature, viz. to 1956, and 1957—61 respectively. Newly isolated monoterpenoids now occupy a class of their own in the first supplement, although some cycloheptane monoterpenoids e.g. /8-dolabrin), quinones e.g. /S-thujaplicinol), and tetrahydrocannabinol (the formula is incorrect) are listed separately. 

Although chemical research on marijuana began over 150 years ago, it wasn t until 1964 that the first authenticated isolation of a pure, active principle delta-one tetrahydrocannabinol (A -THC) was achieved, and not until 1970 that it was determined to be the only major psychoactive component. Even though dozens of cannabinoids have been isolated since then, none have been found to be significantly psychoactive. 

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