METABOLISM OF THE PSYCHOTOMIMETIC TRYPTAMINE DERIVATIVE 5-METHOXY-N,N-DIISOPROPYLTRYPTAMINE IN HUMANS: IDENTIFICATION AND QUANTIFICATION OF ITS URINARY METABOLITES

Abstract

ABSTRACT:The urinary metabolites of 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) in humans have been investigated by analyzing urine specimens from its users. For the unequivocal identification and accurate quantification of its major metabolites, careful analyses were conducted by gas chromatography/mass spectrometry, liquid chromatography/mass spectrometry, and liquid chromatography-tandem mass spectrometry, using authentic standards of each metabolite synthesized. Three major metabolic pathways were revealed as follows: 1) side chain degradation by O-demethylation to form 5-hydroxy-N,N-diisopropyltryptamine (5-OH-DIPT), which would be partly conjugated to its sulfate and glucuronide; 2) direct hydroxylation on position 6 of the aromatic ring of 5-MeO-DIPT, and/or methylation of the hydroxyl group on position 5 after hydroxylation on position 6 of the aromatic ring of 5-OH-DIPT, to produce 6-hydroxy-5-methoxy-N,N-diisopropyltryptamine (6-OH-5-MeO-DIPT), followed by conjugation to its sulfate and glucuronide; and 3) side chain degradation by N-deisopropylation, to the corresponding secondary amine 5-methoxy-N-isopropyltryptamine (5-MeO-NIPT). Of these metabolites, which retain structural characteristics of the parent drug, 5-OH-DIPT and 6-OH-5-MeO-DIPT were found to be more abundant than 5-MeO-NIPT. Although the parent drug 5-MeO-DIPT was detectable even 35 h after dosing, no trace of its N-oxide was detected in any of the specimens examined.

Urinary Excretion Profiles of 5-Methoxy-N,N-diisopropyltryptamine and Its Relevant Metabolites in Humans

“…Urine Specimens from 5-MeO-DIPT Users --Eleven urine specimens were voluntarily provided from six 5-MeO-DIPT users (Users A-F). Users A and B are identical with Users A and B in our previous paper, 5) respectively. Additional specimens from these users were analyzed in the present study.…”

“…5) The internal standard (I.S.) 5-methyltryptamine (5-MT) hydrochloride was purchased from SigmaAldrich (St. Louis, MO, U.S.A.).…”

“…Extraction of 5-MeO-DIPT and Its Metabolites --Liquid-liquid extraction: Liquid-liquid extraction was carried out with a chloroformisopropyl alcohol mixture (3 : 1, v/v) as previously described. 5) The residue obtained was dissolved in methanol for GC/MS or the initial mobile phase for LC/MS, and was subjected to the respective systems.…”

“…5) TMS Derivatization for GC/MS --Methanolic solutions of each synthesized standards and the extracts of urine specimens were transferred into screw-capped glass vials. These were evaporated to dryness under a gentle stream of nitrogen at 40 • C. After the addition of MSTFA, the vials were capped and heated at 60 • C for 30 min.…”

“…5) The metabolites identified are: 5-hydroxy-N,N-diisopropyltryptamine (5-OH-DIPT), demethylated metabolite; 6-hydroxy-5-methoxy-N,N-diisopropyltryptamine (6-OH-5-MeO-DIPT), aromatic ring hydroxylated metabolite; and 5-methoxy-N-isopropyltryptamine (5-MeO-NIPT), deisopropylated metabolite. Figure 1 shows their chemical structures.…”