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.

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.

Study at a glance

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.