Metabolism of the tryptamine-derived new psychoactive substances 5-MeO-2-Me-DALT, 5-MeO-2-Me-ALCHT, and 5-MeO-2-Me-DIPT and their detectability in urine studied by GC-MS, LC-MSn, and LC-HR-MS/MS.
Many N,N-dialkylated tryptamines show psychoactive properties and were encountered as new psychoactive substances. The aims of the presented work were to study the phase I and II metabolism and the detectability in standard urine screening approaches (SUSA) of 5-methoxy-2-methyl-N,N-diallyltryptamine (5-MeO-2-Me-DALT), 5-methoxy-2-methyl-N-allyl-N-cyclohexyltryptamine (5-MeO-2-Me-ALCHT), and 5-methoxy-2-methyl-N,N-diisopropyltryptamine (5-MeO-2-Me-DIPT) using gas chromatography-mass spectrometry (GC-MS), liquid chromatography coupled with multistage accurate mass spectrometry (LC-MSn), and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS). For metabolism studies, urine was collected over a 24 h period after administration of the compounds to male Wistar rats at 20 mg/kg body weight (BW). Phase I and II metabolites were identified after urine precipitation with acetonitrile by LC-HR-MS/MS. 5-MeO-2-Me-DALT (24 phase I and 12 phase II metabolites), 5-MeO-2-Me-ALCHT (24 phase I and 14 phase II metabolites), and 5-MeO-2-Me-DIPT (20 phase I and 11 phase II metabolites) were mainly metabolized by O-demethylation, hydroxylation, N-dealkylation, and combinations of them as well as by glucuronidation and sulfation of phase I metabolites. Incubations with mixtures of pooled human liver microsomes and cytosols (pHLM and pHLC) confirmed that the main metabolic reactions in humans and rats might be identical. Furthermore, initial CYP activity screenings revealed that CYP1A2, CYP2C19, CYP2D6, and CYP3A4 were involved in hydroxylation, CYP2C19 and CYP2D6 in O-demethylation, and CYP2C19, CYP2D6, and CYP3A4 in N-dealkylation. For SUSAs, GC-MS, LC-MSn, and LC-HR-MS/MS were applied to rat urine samples after 1 or 0.1 mg/kg BW doses, respectively. In contrast to the GC-MS SUSA, both LC-MS SUSAs were able to detect an intake of 5-MeO-2-Me-ALCHT and 5-MeO-2-Me-DIPT via their metabolites following 1 mg/kg BW administrations and 5-MeO-2-Me-DALT following 0.1 mg/kg BW dosage. Copyright © 2017 John Wiley & Sons, Ltd.
Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical, Pharmacology and Toxicology, Saarland University, Kirrberger Str. 100, Building 46, D-66421, Homburg (Saar), Germany.
Achim T
AT
Caspar
Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical, Pharmacology and Toxicology, Saarland University, Kirrberger Str. 100, Building 46, D-66421, Homburg (Saar), Germany.
Jonas B
JB
Gaab
Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical, Pharmacology and Toxicology, Saarland University, Kirrberger Str. 100, Building 46, D-66421, Homburg (Saar), Germany.
Julian A
JA
Michely
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, James, Parsons Building, Byrom Street, Liverpool, L3 3AF, UK.|The Alexander Shulgin Research Institute, 1483 Shulgin Road, Lafayette, CA, 94549, USA.
Simon D
http://orcid.org/0000-0001-8632-5372
SD
Brandt
Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical, Pharmacology and Toxicology, Saarland University, Kirrberger Str. 100, Building 46, D-66421, Homburg (Saar), Germany.
Markus R
http://orcid.org/0000-0003-4377-6784
MR
Meyer
Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical, Pharmacology and Toxicology, Saarland University, Kirrberger Str. 100, Building 46, D-66421, Homburg (Saar), Germany.
Hans H
http://orcid.org/0000-0003-4579-4660
HH
Maurer
D008735:5-Methoxytryptamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D000498:Allyl Compounds / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D002853:Chromatography, Liquid / Q000379:methods / Q000592:standards; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods* / Q000592:standards; D006801:Humans; D011619:Psychotropic Drugs / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D015813:Substance Abuse Detection / Q000379:methods / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards; D014363:Tryptamines / Q000737:chemistry / Q000378:metabolism* / Q000652:urine
C487455:5-methoxy-N,N-diisopropyltryptamine N-oxide; D000498:Allyl Compounds; D003497:Cyclic N-Oxides; D011619:Psychotropic Drugs; D014363:Tryptamines; D008735:5-Methoxytryptamine; C030820:tryptamine; C578955:N,N-diallyl-5-methoxytryptamine
LC-HR-MS/MS; LC-MSn; cytochrome-P450; metabolism; new psychoactive substances; tryptamines