Studies on the metabolism of the Δ9-tetrahydrocannabinol precursor Δ9-tetrahydrocannabinolic acid A (Δ9-THCA-A) in rat using LC-MS/MS, LC-QTOF MS and GC-MS techniques
Article first published online: 2 SEP 2009
Copyright © 2009 John Wiley & Sons, Ltd.
Journal of Mass Spectrometry
Volume 44, Issue 10, pages 1423–1433, October 2009
How to Cite
Jung, J., Meyer, M. R., Maurer, H. H., Neusüß, C., Weinmann, W. and Auwärter, V. (2009), Studies on the metabolism of the Δ9-tetrahydrocannabinol precursor Δ9-tetrahydrocannabinolic acid A (Δ9-THCA-A) in rat using LC-MS/MS, LC-QTOF MS and GC-MS techniques. J. Mass Spectrom., 44: 1423–1433. doi: 10.1002/jms.1624
- Issue published online: 9 OCT 2009
- Article first published online: 2 SEP 2009
- Manuscript Accepted: 9 JUL 2009
- Manuscript Received: 27 OCT 2008
- Δ9-Tetrahydrocannabinolic acid-A (Δ9-THCA-A);
- LC-QTOF MS;
In Cannabis sativa, Δ9-Tetrahydrocannabinolic acid-A (Δ9-THCA-A) is the non-psychoactive precursor of Δ9-tetrahydrocannabinol (Δ9-THC). In fresh plant material, about 90% of the total Δ9-THC is available as Δ9-THCA-A. When heated (smoked or baked), Δ9-THCA-A is only partially converted to Δ9-THC and therefore, Δ9-THCA-A can be detected in serum and urine of cannabis consumers. The aim of the presented study was to identify the metabolites of Δ9-THCA-A and to examine particularly whether oral intake of Δ9-THCA-A leads to in vivo formation of Δ9-THC in a rat model. After oral application of pure Δ9-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 Δ9-THC and its metabolites, urine extracts were analyzed by gas chromatography-mass spectrometry (GC-MS). The identified metabolites show that Δ9-THCA-A undergoes a hydroxylation in position 11 to 11-hydroxy-Δ9-tetrahydrocannabinolic acid-A (11-OH-Δ9-THCA-A), which is further oxidized via the intermediate aldehyde 11-oxo-Δ9-THCA-A to 11-nor-9-carboxy-Δ9-tetrahydrocannabinolic acid-A (Δ9-THCA-A-COOH). Glucuronides of the parent compound and both main metabolites were identified in the rat urine as well. Furthermore, Δ9-THCA-A undergoes hydroxylation in position 8 to 8-alpha- and 8-beta-hydroxy-Δ9-tetrahydrocannabinolic acid-A, respectively, (8α-Hydroxy-Δ9-THCA-A and 8β-Hydroxy-Δ9-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 Δ9-THCA-A to Δ9-THC was not observed. Copyright © 2009 John Wiley & Sons, Ltd.