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.
Footnotes
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This study was supported by a grant-in-aid from Japan Society for the Promotion of Science (No. 16915019).
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.105.005835.
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ABBREVIATIONS: 5-MeO-DIPT, 5-methoxy-N,N-diisopropyltryptamine; DMT, dimethyltryptamine; EI, electron ionization; ESI, electrospray ionization; GC, gas chromatography; I.S., internal standard; LC, liquid chromatography; 5-MeO-DMT, 5-methoxy-N,N-dimethyltryptamine; 5-MeO-DIPT-NO, 5-methoxy-N,N-diisopropyltryptamine-N-oxide; 5-MeO-NIPT, 5-methoxy-N-isopropyltryptamine; MS, mass spectrometry; MS/MS, tandem mass spectrometry; MSTFA, N-methyl-N-trimethylsilyltrifluoroacetamide; 5-MT, 5-methyltryptamine; 5-OH-DIPT, 5-hydroxy-N,N-diisopropyltryptamine; 6-OH-5-MeO-DIPT, 6-hydroxy-5-methoxy-N,N-diisopropyltryptamine; THF, tetrahydrofuran; TMS, trimethylsilyl.
- Received June 15, 2005.
- Accepted November 7, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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