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.
Talanta
October 1, 2018
Achim T Caspar, Markus R Meyer, Folker Westphal et al.
17 citations
Two new hallucinogens, 3,4-DMA-NBOMe and 4-MMA-NBOMe, are extensively metabolized in rats and human liver preparations. Using nano liquid chromatography with high-resolution mass spectrometry, 38 metabolites of 3,4-DMA-NBOMe and 33 metabolites of 4-MMA-NBOMe were identified. The main metabolic pathways are O-demethylation and glucuronic acid conjugation for 3,4-DMA-NBOMe, and oxidation of the tolyl group to carboxylic acid for 4-MMA-NBOMe. The nanoLC approach performed comparably to conventional UHPLC. Standard urine screening methods could detect an estimated low user dose only through metabolites. Suggested screening targets include O-demethyl- and O,O-bis-demethyl-3,4-DMA-NBOMe and their glucuronides, and carboxy-4-MMA-NBOMe and its glucuronide and N-demethyl-carboxy-4-MMA-NBOMe.
Toxicology letters
March 15, 2018
Achim T Caspar, Markus R Meyer, Hans H Maurer
Six NBOMe-derived new psychoactive substances (25B-, 25C-, 25I-, 3,4-DMA-, 4-EA-, and 4-MMA-NBOMe) are metabolized by multiple cytochrome P450 enzymes, primarily CYP2D6 and CYP2C19. Michaelis-Menten kinetic constants were determined using the substrate depletion approach; Km values ranged from 0.010 μM (CYP2D6, 4-MMA-NBOMe) to 13 μM (CYP2B6, 4-EA-NBOMe). CYP2D6 contributed most to hepatic net clearance for five compounds (61–89%), while CYP2C19 dominated for 4-MMA-NBOMe (64%). Because multiple isoforms are involved, the risk of drug-drug interactions may be low, but inter-individual variation in metabolism is possible for substances highly dependent on polymorphic CYP2C19 or CYP2D6.