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1000
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Abstract/Summary
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(-)-Δ-9-tetrahydrocannabinol ((-)-Δ-9-THC) is the main psychoactive constituent in cannabis. During phase I metabolism, it is metabolized to (-)-11-hydroxy-Δ-9-tetrahydrocannabinol ((-)-11-OH-Δ-9-THC), which is psychoactive, and to (-)-11-nor-9-carboxy-Δ-9-tetrahydrocannabinol ((-)-Δ-9-THC-COOH), which is psychoinactive. It is glucuronidated during phase II metabolism. The biotransformation of (-)-Δ-9-tetrahydrocannabinol-glucuronide ((-)-Δ-9-THC-Glc) and (-)-11-nor-9-carboxy-Δ-9-tetrahydrocannabinol-glucuronide ((-)-Δ-9-THC-COOH-Glc) is well understood, which is mainly due to the availability of commercial reference standards. Since such a standardized reference is not yet available for (-)-11-hydroxy-Δ-9-tetrahydrocannabinol-glucuronide ((-)-11-OH-Δ-9-THC-Glc), its biotransformation is harder to study and the nature of the glucuronide bonding-alcoholic and/or phenolic-remains unclear. Consequently, the aim of this study was to investigate the biotransformation of (-)-11-OH-Δ-9-THC-Glc in vitro as well as in vivo and to identify the glucuronide by chemically synthesis of a reference standard. For in vitro analysis, pooled human S9 liver fraction was incubated with (-)-Δ-9-THC. Resulting metabolites were detected by high-performance liquid chromatography system coupled to a high-resolution mass spectrometer (HPLC-HRMS) with heated electrospray ionization (HESI) in positive and negative full scan mode. Five different chromatographic peaks of OH-Δ-9-THC-Glc have been detected in HESI positive and negative mode, respectively. The experiment set up according to Wen et al. indicates the two main metabolites being an alcoholic and a phenolic glucuronide metabolite. In vivo analysis of urine (n = 10) and serum (n = 10) samples from cannabis users confirmed these two main metabolites. Thus, OH-Δ-9-THC is glucuronidated at either the phenolic or the alcoholic hydroxy group. A double glucuronidation was not observed. The alcoholic (-)-11-OH-Δ-9-THC-Glc was successfully chemically synthesized and identified the main alcoholic glucuronide in vitro and in vivo. (-)-11-OH-Δ-9-THC-Glc is the first reference standard for direct identification and quantification. This enables future research to answer the question whether phenolic or alcoholic glucuronidation forms the predominant way of metabolism.
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1000
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Hinweis
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DeepGreen-ID: bd6ec30f93914729bc4278b2dbc684d2 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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