title: Biotransformation and detectability of the new psychoactive substances N,N-diallyltryptamine (DALT) derivatives 5-fluoro-DALT, 7-methyl-DALT, and 5,6-methylenedioxy-DALT in urine using GC-MS, LC-MSn, and LC-HR-MS/MS.
abstract: Derivatives of N,N-diallyltryptamine (DALT) can be classified as new psychoactive substances. Biotransformation and detectability of 5-fluoro-DALT (5-F-DALT), 7-methyl-DALT (7-Me-DALT), and 5,6-methylenedioxy-DALT (5,6-MD-DALT) are described here. Their metabolites detected in rat urine and pooled human liver microsomes were identified by liquid chromatography (LC)-high resolution (HR)-tandem mass spectrometry (MS/MS). In addition, the human cytochrome-P450 (CYP) isoenzymes involved in the main metabolic steps were identified and detectability tested in urine by the authors' urine screening approaches using GC-MS, LC-MSn, or LC-HR-MS/MS. Aromatic and aliphatic hydroxylations, N-dealkylation, N-oxidation, and combinations could be proposed for all compounds as main pathways. Carboxylation after initial hydroxylation of the methyl group could also be detected for 7-Me-DALT and O-demethylenation was observed for 5,6-MD-DALT. All phase I metabolites were extensively glucuronidated or sulfated. Initial phase I reactions were catalyzed by CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5. Rat urine samples were analyzed following two different low-dose administrations. GC-MS was not able to monitor consumption reliably, but all three compounds are predicted to be detectable in cases of overdose. The LC-MSnand LC-HR-MS/MS approaches were suitable for detecting an intake of all three compounds mainly via their metabolites. However, after the lowest dose, a reliable monitoring could only be achieved for 5-F-DALT via LC-MSnand LC-HR-MS/MS and for 7-Me-DALT via LC-HR-MS/MS. The most abundant targets in both LC-MS screenings were one of two hydroxy-aryl metabolites and both corresponding glucuronides for 5-F-DALT, one N-deallyl hydroxy-aryl, the carboxy, and one dihydroxy-aryl metabolite for 7-Me-DALT, and the demethylenyl metabolite, its oxo metabolite, and glucuronide for 5,6-MD-DALT.
authors.affiliation: Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421, Homburg, Saar, Germany.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Michely
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK.|The Alexander Shulgin Research Institute, 1483 Shulgin Road, Lafayette, CA, 94549, USA.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Brandt
authors.affiliation: Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421, Homburg, Saar, Germany.
authors.forename: Markus R
authors.initials: MR
authors.lastname: Meyer
authors.affiliation: Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421, Homburg, Saar, Germany. hans.maurer@uks.eu.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Maurer
mesh_terms: D000818:Animals; D001711:Biotransformation; D002853:Chromatography, Liquid / Q000379:methods; D015198:Designer Drugs / Q000032:analysis / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D054879:Halogenation; D006801:Humans; D013287:Illicit Drugs / Q000378:metabolism / Q000652:urine*; D008297:Male; D008745:Methylation; D008862:Microsomes, Liver / Q000378:metabolism; D011619:Psychotropic Drugs / Q000378:metabolism / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D015813:Substance Abuse Detection / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014363:Tryptamines / Q000378:metabolism / Q000652:urine*
chemical_list: D015198:Designer Drugs; D013287:Illicit Drugs; D011619:Psychotropic Drugs; D014363:Tryptamines
keywords: 5,6-MD-DALT; 5-F-DALT; 7-Me-DALT; Metabolism; Screening; Tryptamine derivatives