Analytical and Bioanalytical Chemistry
June 24, 2015
Achim T. Caspar, Andreas G. Helfer, Julian A Michely et al.
69 citations
25I-NBOMe, a potent hallucinogenic drug that activates 5-HT2A receptors, is extensively metabolized in rats. After administration to male Wistar rats, 68 metabolites were identified in urine using liquid chromatography-high-resolution tandem mass spectrometry. The main metabolic pathways include O-demethylation, O,O-bis-demethylation, hydroxylation, and combinations, followed by glucuronidation and sulfation. Detection of intake is possible through metabolites using LC-MS methods but not by GC-MS standard urine screening. Initial tests indicate that CYP1A2 and CYP3A4 are involved in hydroxylation, while CYP2C9 and CYP2C19 mediate O-demethylation, suggesting potential drug-drug interactions.
Analytical and Bioanalytical Chemistry
October 1, 2015
Julian A Michely, Andreas G. Helfer, Simon D. Brandt et al.
49 citations
N,N-Diallyltryptamine (DALT) and 5-methoxy-DALT (5-MeO-DALT) are synthetic tryptamines with psychoactive effects. In rats, after high-dose administration, their metabolism involves aromatic and aliphatic hydroxylations, N-dealkylation, N-oxidation, and combinations; 5-MeO-DALT also undergoes O-demethylation, followed by extensive glucuronidation or sulfation. The main cytochrome P450 enzymes for DALT are CYP2C19, CYP2D6, and CYP3A4; for 5-MeO-DALT, CYP1A2, CYP2C19, CYP2D6, and CYP3A4. For detecting low-dose consumption in rat urine, LC-MS(n) and LC-HR-MS-MS are suitable; the most abundant markers are a ring hydroxy metabolite of DALT, the N,O-bis-dealkyl metabolite of 5-MeO-DALT, and their glucuronides. GC-MS can screen DALT only via its main metabolites.
Current Neuropharmacology
November 3, 2016
Julian A Michely, Sascha K. Manier, Achim T. Caspar et al.
36 citations
Two new psychoactive substances, 3-MeO-PCP and 3-MeOPCPy, are metabolized in rat and human liver microsomes through multiple pathways including hydroxylation, O-demethylation, and glucuronidation. Specific cytochrome P450 enzymes (CYP 2B6, 2C19, 2C9, 2D6) catalyze initial metabolic steps. Because only polymorphically expressed enzymes are involved, pharmacogenomic variations may affect metabolism, though clinical data are needed to confirm relevance. Standard urine screening approaches using GC-MS, LC-MSn, and LC-HR-MS/MS can detect intake of both drugs via identified metabolites.
Drug Testing and Analysis
January 1, 2018
Achim T. Caspar, Jonas B Gaab, Julian A Michely et al.
33 citations
Three new psychoactive tryptamines—5-MeO-2-Me-DALT, 5-MeO-2-Me-ALCHT, and 5-MeO-2-Me-DIPT—are mainly broken down in the body through O-demethylation, hydroxylation, and N-dealkylation, followed by glucuronidation or sulfation. In rats given 20 mg/kg doses, 5-MeO-2-Me-DALT produced 24 phase I and 12 phase II metabolites, 5-MeO-2-Me-ALCHT produced 24 phase I and 14 phase II metabolites, and 5-MeO-2-Me-DIPT produced 20 phase I and 11 phase II metabolites. Human liver enzyme incubations suggest the same major metabolic pathways occur in humans. CYP1A2, CYP2C19, CYP2D6, and CYP3A4 catalyze hydroxylation; CYP2C19 and CYP2D6 catalyze O-demethylation; and CYP2C19, CYP2D6, and CYP3A4 catalyze N-dealkylation. Liquid chromatography-based urine screening detected intake of all three compounds after low doses (0.1–1 mg/kg), whereas gas chromatography-based screening did not.
Analytical and Bioanalytical Chemistry
February 1, 2017
Julian A Michely, Simon D. Brandt, Markus R Meyer et al.
23 citations
Derivatives of N,N-diallyltryptamine (DALT) are new psychoactive substances. Their metabolism and detectability were studied in rat urine and human liver microsomes using liquid chromatography-high resolution-tandem mass spectrometry. Main metabolic pathways include aromatic and aliphatic hydroxylations, N-dealkylation, N-oxidation, and combinations; carboxylation was detected for 7-Me-DALT and O-demethylenation for 5,6-MD-DALT. Phase I metabolites were extensively glucuronidated or sulfated, catalyzed by several CYP isoenzymes. GC-MS could not reliably monitor consumption, but LC-MSn and LC-HR-MS/MS approaches were suitable, especially for detecting 5-F-DALT and 7-Me-DALT at low doses. The most abundant targets for each compound are specified.