Please use this identifier to cite or link to this item: doi:10.22028/D291-34588
Title: In Vitro Metabolic Fate of the Synthetic Cannabinoid Receptor Agonists QMPSB and QMPCB (SGT-11) Including Isozyme Mapping and Esterase Activity
Author(s): Richter, Matthias J.
Wagmann, Lea
Gampfer, Tanja M.
Brandt, Simon D.
Meyer, Markus R.
Language: English
Title: Metabolites
Volume: 11
Issue: 8
Publisher/Platform: MDPI
Year of Publication: 2021
Free key words: QMPSB
synthetic cannabinoid receptor agonists
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Quinolin-8-yl 4-methyl-3-(piperidine-1-sulfonyl)benzoate (QMPSB) and quinolin-8-yl 4- methyl-3-(piperidine-1-carbonyl)benzoate (QMPCB, SGT-11) are synthetic cannabinoid receptor agonists (SCRAs). Knowing their metabolic fate is crucial for the identification of toxicological screening targets and to predict possible drug interactions. The presented study aimed to identify the in vitro phase I/II metabolites of QMPSB and QMPCB and to study the contribution of different monooxygenases and human carboxylesterases by using pooled human liver S9 fraction (pHLS9), recombinant human monooxygenases, three recombinant human carboxylesterases, and pooled human liver microsomes. Analyses were carried out by liquid chromatography high-resolution tandem mass spectrometry. QMPSB and QMPCB showed ester hydrolysis, and hydroxy and carboxylic acid products were detected in both cases. Mono/dihydroxy metabolites were formed, as were corresponding glucuronides and sulfates. Most of the metabolites could be detected in positive ionization mode with the exception of some QMPSB metabolites, which could only be found in negative mode. Monooxygenase activity screening revealed that CYP2B6/CYP2C8/CYP2C9/CYP2C19/CYP3A4/CYP3A5 were involved in hydroxylations. Esterase screening showed the involvement of all investigated isoforms. Additionally, extensive non-enzymatic ester hydrolysis was observed. Considering the results of the in vitro experiments, inclusion of the ester hydrolysis products and their glucuronides and monohydroxy metabolites into toxicological screening procedures is recommended.
DOI of the first publication: 10.3390/metabo11080509
Link to this record: urn:nbn:de:bsz:291--ds-345882
ISSN: 2218-1989
Date of registration: 27-Aug-2021
Description of the related object: Supplementary Materials
Related object:
Faculty: M - Medizinische Fakultät
Department: M - Experimentelle und Klinische Pharmakologie und Toxikologie
Professorship: M - Prof. Dr. Markus Meyer
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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