Metabolism of the new psychoactive substances N,N-diallyltryptamine (DALT) and 5-methoxy-DALT and their detectability in urine by GC-MS, LC-MSn, and LC-HR-MS-MS.
Julian A Michely, Andreas G Helfer, Simon D Brandt, Markus R Meyer, Hans H Maurer
Analytical and bioanalytical chemistry October 1, 2015 Peer reviewed DOI: 10.1007/s00216-015-8955-0 via PubMed
Summary
DALT and 5-MeO-DALT, synthetic tryptamine derivatives, undergo various metabolic processes in rats, including hydroxylation and N-dealkylation. Key cytochrome P450 enzymes involved in DALT metabolism include CYP2C19, CYP2D6, and CYP3A4, while CYP1A2 also plays a role in 5-MeO-DALT metabolism. For detectability, liquid chromatography methods were effective in monitoring both compounds in urine after low-dose administration.
Study at a glance
| Population | rat subjects |
|---|---|
| Key finding | DALT and 5-MeO-DALT are metabolized through several pathways, with specific cytochrome P450 enzymes being predominantly involved. |
Abstract
N,N-Diallyltryptamine (DALT) and 5-methoxy-DALT (5-MeO-DALT) are synthetic tryptamine derivatives commonly referred to as so-called new psychoactive substances (NPS). They have psychoactive effects that may be similar to those of other tryptamine derivatives. The objectives of this work were to study the metabolic fate and detectability, in urine, of DALT and 5-MeO-DALT. For metabolism studies, rat urine obtained after high-dose administration was prepared by precipitation and analyzed by liquid chromatography-high-resolution mass spectrometry (LC-HR-MS-MS). On the basis of the metabolites identified, several aromatic and aliphatic hydroxylations, N-dealkylation, N-oxidation, and combinations thereof are proposed as the main metabolic pathways for both compounds. O-Demethylation of 5-MeO-DALT was also observed, in addition to extensive glucuronidation or sulfation of both compounds after phase I transformation. The cytochrome P450 (CYP) isoenzymes predominantly involved in DALT metabolism were CYP2C19, CYP2D6, and CYP3A4; those mainly involved in 5-MeO-DALT metabolism were CYP1A2, CYP2C19, CYP2D6, and CYP3A4. For detectability studies, rat urine was screened by GC-MS, LC-MS(n), and LC-HR-MS-MS after administration of low doses. LC-MS(n) and LC-HR-MS-MS were deemed suitable for monitoring consumption of both compounds. The most abundant targets were a ring hydroxy metabolite of DALT, the N,O-bis-dealkyl metabolite of 5-MeO-DALT, and their glucuronides. GC-MS enabled screening of DALT by use of its main metabolites only.