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Studies on the metabolism of the Delta9-tetrahydrocannabinol precursor Delta9-tetrahydrocannabinolic acid A (Delta9-THCA-A) in rat using LC-MS/MS, LC-QTOF MS and GC-MS techniques.
J Mass Spectrom. 2009 Oct; 44(10):1423-33.JM

Abstract

In Cannabis sativa, Delta9-Tetrahydrocannabinolic acid-A (Delta9-THCA-A) is the non-psychoactive precursor of Delta9-tetrahydrocannabinol (Delta9-THC). In fresh plant material, about 90% of the total Delta9-THC is available as Delta9-THCA-A. When heated (smoked or baked), Delta9-THCA-A is only partially converted to Delta9-THC and therefore, Delta9-THCA-A can be detected in serum and urine of cannabis consumers. The aim of the presented study was to identify the metabolites of Delta9-THCA-A and to examine particularly whether oral intake of Delta9-THCA-A leads to in vivo formation of Delta9-THC in a rat model. After oral application of pure Delta9-THCA-A to rats (15 mg/kg body mass), urine samples were collected and metabolites were isolated and identified by liquid chromatography-mass spectrometry (LC-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high resolution LC-MS using time of flight-mass spectrometry (TOF-MS) for accurate mass measurement. For detection of Delta9-THC and its metabolites, urine extracts were analyzed by gas chromatography-mass spectrometry (GC-MS). The identified metabolites show that Delta9-THCA-A undergoes a hydroxylation in position 11 to 11-hydroxy-Delta9-tetrahydrocannabinolic acid-A (11-OH-Delta9-THCA-A), which is further oxidized via the intermediate aldehyde 11-oxo-Delta9-THCA-A to 11-nor-9-carboxy-Delta9-tetrahydrocannabinolic acid-A (Delta9-THCA-A-COOH). Glucuronides of the parent compound and both main metabolites were identified in the rat urine as well. Furthermore, Delta9-THCA-A undergoes hydroxylation in position 8 to 8-alpha- and 8-beta-hydroxy-Delta9-tetrahydrocannabinolic acid-A, respectively, (8alpha-Hydroxy-Delta9-THCA-A and 8beta-Hydroxy-Delta9-THCA-A, respectively) followed by dehydration. Both monohydroxylated metabolites were further oxidized to their bishydroxylated forms. Several glucuronidation conjugates of these metabolites were identified. In vivo conversion of Delta9-THCA-A to Delta9-THC was not observed.

Authors+Show Affiliations

Institute of Forensic Medicine, Forensic Toxicology, University Medical Centre Freiburg, D-79104 Freiburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19728318

Citation

Jung, Julia, et al. "Studies On the Metabolism of the Delta9-tetrahydrocannabinol Precursor Delta9-tetrahydrocannabinolic Acid a (Delta9-THCA-A) in Rat Using LC-MS/MS, LC-QTOF MS and GC-MS Techniques." Journal of Mass Spectrometry : JMS, vol. 44, no. 10, 2009, pp. 1423-33.
Jung J, Meyer MR, Maurer HH, et al. Studies on the metabolism of the Delta9-tetrahydrocannabinol precursor Delta9-tetrahydrocannabinolic acid A (Delta9-THCA-A) in rat using LC-MS/MS, LC-QTOF MS and GC-MS techniques. J Mass Spectrom. 2009;44(10):1423-33.
Jung, J., Meyer, M. R., Maurer, H. H., Neusüss, C., Weinmann, W., & Auwärter, V. (2009). Studies on the metabolism of the Delta9-tetrahydrocannabinol precursor Delta9-tetrahydrocannabinolic acid A (Delta9-THCA-A) in rat using LC-MS/MS, LC-QTOF MS and GC-MS techniques. Journal of Mass Spectrometry : JMS, 44(10), 1423-33. https://doi.org/10.1002/jms.1624
Jung J, et al. Studies On the Metabolism of the Delta9-tetrahydrocannabinol Precursor Delta9-tetrahydrocannabinolic Acid a (Delta9-THCA-A) in Rat Using LC-MS/MS, LC-QTOF MS and GC-MS Techniques. J Mass Spectrom. 2009;44(10):1423-33. PubMed PMID: 19728318.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Studies on the metabolism of the Delta9-tetrahydrocannabinol precursor Delta9-tetrahydrocannabinolic acid A (Delta9-THCA-A) in rat using LC-MS/MS, LC-QTOF MS and GC-MS techniques. AU - Jung,Julia, AU - Meyer,Markus R, AU - Maurer,Hans H, AU - Neusüss,Christian, AU - Weinmann,Wolfgang, AU - Auwärter,Volker, PY - 2009/9/4/entrez PY - 2009/9/4/pubmed PY - 2009/12/23/medline SP - 1423 EP - 33 JF - Journal of mass spectrometry : JMS JO - J Mass Spectrom VL - 44 IS - 10 N2 - In Cannabis sativa, Delta9-Tetrahydrocannabinolic acid-A (Delta9-THCA-A) is the non-psychoactive precursor of Delta9-tetrahydrocannabinol (Delta9-THC). In fresh plant material, about 90% of the total Delta9-THC is available as Delta9-THCA-A. When heated (smoked or baked), Delta9-THCA-A is only partially converted to Delta9-THC and therefore, Delta9-THCA-A can be detected in serum and urine of cannabis consumers. The aim of the presented study was to identify the metabolites of Delta9-THCA-A and to examine particularly whether oral intake of Delta9-THCA-A leads to in vivo formation of Delta9-THC in a rat model. After oral application of pure Delta9-THCA-A to rats (15 mg/kg body mass), urine samples were collected and metabolites were isolated and identified by liquid chromatography-mass spectrometry (LC-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high resolution LC-MS using time of flight-mass spectrometry (TOF-MS) for accurate mass measurement. For detection of Delta9-THC and its metabolites, urine extracts were analyzed by gas chromatography-mass spectrometry (GC-MS). The identified metabolites show that Delta9-THCA-A undergoes a hydroxylation in position 11 to 11-hydroxy-Delta9-tetrahydrocannabinolic acid-A (11-OH-Delta9-THCA-A), which is further oxidized via the intermediate aldehyde 11-oxo-Delta9-THCA-A to 11-nor-9-carboxy-Delta9-tetrahydrocannabinolic acid-A (Delta9-THCA-A-COOH). Glucuronides of the parent compound and both main metabolites were identified in the rat urine as well. Furthermore, Delta9-THCA-A undergoes hydroxylation in position 8 to 8-alpha- and 8-beta-hydroxy-Delta9-tetrahydrocannabinolic acid-A, respectively, (8alpha-Hydroxy-Delta9-THCA-A and 8beta-Hydroxy-Delta9-THCA-A, respectively) followed by dehydration. Both monohydroxylated metabolites were further oxidized to their bishydroxylated forms. Several glucuronidation conjugates of these metabolites were identified. In vivo conversion of Delta9-THCA-A to Delta9-THC was not observed. SN - 1096-9888 UR - https://www.unboundmedicine.com/medline/citation/19728318/Studies_on_the_metabolism_of_the_Delta9_tetrahydrocannabinol_precursor_Delta9_tetrahydrocannabinolic_acid_A__Delta9_THCA_A__in_rat_using_LC_MS/MS_LC_QTOF_MS_and_GC_MS_techniques_ L2 - https://doi.org/10.1002/jms.1624 DB - PRIME DP - Unbound Medicine ER -