Phase I metabolism of the carbazole-derived synthetic cannabinoids EG-018, EG-2201, and MDMB-CHMCZCA and detection in human urine samples
Lukas Mogler, Florian Franz, Maurice Wilde, Laura M Huppertz, Sebastian Halter, Verena Angerer, Björn Moosmann & Volker Auwärter
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abstract
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Synthetic cannabinoids (SCs) are a structurally diverse class of new
psychoactive substances. Most SCs used for recreational purposes are
based on indole or indazole core structures. EG-018
(naphthalen-1-yl(9-pentyl-9H-carbazol-3-yl)methanone), EG-2201
((9-(5-fluoropentyl)-9H-carbazol-3-yl)(naphthalen-1-yl)methanone),
and MDMB-CHMCZCA (methyl
2-(9-(cyclohexylmethyl)-9H-carbazole-3-carboxamido)-3,3-dimethylbuta
noate)
are 3 representatives of a structural subclass of SCs, characterized
by a carbazole core system. In vitro and in vivo phase I metabolism
studies were conducted to identify the most suitable metabolites for
the detection of these substances in urine screening. Detection and
characterization of metabolites were performed by liquid
chromatography-electrospray ionization-tandem mass spectrometry
(LC-ESI-MS/MS) and liquid chromatography-electrospray
ionization-quadrupole time-of-flight-mass spectrometry
(LC-ESI-QToF-MS). Eleven in vivo metabolites were detected in urine
samples positive for metabolites of EG-018 (n = 8). A
hydroxypentyl metabolite, most probably the 4-hydroxypentyl isomer,
and an N-dealkylated metabolite mono-hydroxylated at the carbazole
core system were most abundant. In vitro studies of EG-018 and
EG-2201 indicated that oxidative defluorination of the
5-fluoropentyl side chain of EG-2201 as well as dealkylation led to
common metabolites with EG-018. This has to be taken into account
for interpretation of analytical findings. A differentiation between
EG-018 and EG-2201 (n = 1) uptake is possible by the
detection of compound-specific in vivo phase I metabolites evaluated
in this study. Out of 30 metabolites detected in urine samples of
MDMB-CHMCZCA users (n = 20), a metabolite
mono-hydroxylated at the cyclohexyl methyl tail is considered the
most suitable compound-specific consumption marker while a
biotransformation product of mono-hydroxylation in combination with
hydrolysis of the terminal methyl ester function provides best
sensitivity due to its high abundance.
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citation
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Mogler L, Franz F, Wilde M, Huppertz L M, Halter S, Angerer V,
Moosmann B, Auwärter V. Phase I metabolism of the carbazole-derived
synthetic cannabinoids EG-018, EG-2201, and MDMB-CHMCZCA and
detection in human urine samples. Drug Test Anal 2018; 10:1417-1429.
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type
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journal paper/review (English)
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date of publishing
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23-05-2018
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journal title
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Drug Test Anal (10/9)
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ISSN electronic
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1942-7611
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pages
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1417-1429
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PubMed
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29726116
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DOI
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10.1002/dta.2398
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