Metabolism of the new psychoactive substances N,N-diallyltryptamine (DALT) and 5-methoxy-DALT and their detectability in urine by GC–MS, LC–MS

详细信息    查看全文

• 作者：Julian A. Michely ; Andreas G. Helfer…
• 关键词：Designer drugs ; DALT ; 5 ; MeO ; DALT ; Metabolism ; SUSA ; LC–HR–MS–MS
• 刊名：Analytical and Bioanalytical Chemistry
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：407
• 期：25
• 页码：7831-7842
• 全文大小：453 KB
• 参考文献：1.United Nations Office on Drugs and Crime (UNODC) (2014) World Drug Report 2014. http://?www.?unodc.?org/?documents/?data-and-analysis/?WDR2014/?World_?Drug_?Report_-014_?web.?pdf
  2.Brandt SD, King LA, Evans-Brown M (2014) The new drug phenomenon. Drug Test Anal 6:587-97CrossRef
  3.Meyer MR, Caspar A, Brandt SD, Maurer HH (2014) A qualitative/quantitative approach for the detection of 37 tryptamine-derived designer drugs, 5 beta-carbolines, ibogaine, and yohimbine in human urine and plasma using standard urine screening and multi-analyte approaches. Anal Bioanal Chem 406:225-37CrossRef
  4.Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB (2014) Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes. Psychopharmacology (Berl) 231:4135-144CrossRef
  5.Cozzi NV, Gopalakrishnan A, Anderson LL, Feih JT, Shulgin AT, Daley PF, Ruoho AE (2009) Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter. J Neural Transm 116:1591-599CrossRef
  6.Halberstadt AL, Geyer MA (2011) Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology 61:364-81CrossRef
  7.Halberstadt AL, Koedood L, Powell SB, Geyer MA (2011) Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice. J Psychopharmacol 25:1548-561CrossRef
  8.Nichols DE (2012) Structure-activity relationships of serotonin 5-HT2A agonists. WIREs Membr Transport Signaling 1:559-79CrossRef
  9.Shulgin AT (2003) Basic pharmacology and effects. In: Laing R R, Halluinogens A Forensic drug handbook. Elsevier Science, London, 67-37
  10.Shulgin AT, Shulgin A (2004) 5-MeO-DALT. http://?isomerdesign.?com/?PiHKAL/?read.?php??domain=?tk&?id=-6
  11.Shulgin AT, Shulgin A (2004) DALT. http://?isomerdesign.?com/?PiHKAL/?read.?php??domain=?tk&?id=-7
  12.Corkery JM, Durkin E, Elliott S, Schifano F, Ghodse AH (2012) The recreational tryptamine 5-MeO-DALT (N, N-diallyl-5-methoxytryptamine): a brief review. Prog Neuropsychopharmacol Biol Psychiatry 39:259-62CrossRef
  13.Jovel A, Felthous A, Bhattacharyya A (2014) Delirium due to intoxication from the novel synthetic tryptamine 5-MeO-DALT. J Forensic Sci 59:844-46CrossRef
  14.Brandt SD, Martins CPB (2010) Analytical methods for psychoactive N, N-dialkylated tryptamines. Trends Anal Chem 29:858-69CrossRef
  15.Gaujac A, Navickiene S, Collins MI, Brandt SD, de Andrade JB (2012) Analytical techniques for the determination of tryptamines and beta-carbolines in plant matrices and in psychoactive beverages consumed during religious ceremonies and neo-shamanic urban practices. Drug Test Anal 4:636-48CrossRef
  16.Katagi M, Kamata T, Zaitsu K, Shima N, Kamata H, Nakanishi K, Nishioka H, Miki A, Tsuchihashi H (2010) Metabolism and toxicologic analysis of tryptamine-derived drugs of abuse. Ther Drug Monit 32:328-31CrossRef
  17.Brandt SD, Tirunarayanapuram SS, Freeman S, Dempster N, Barker SA, Daley PF, Cozzi NV, Martins CPB (2008) Microwave-accelerated synthesis of psychoactive deuterated N, N-dialkylated-[alpha, alpha, beta, beta-d(4)]-tryptamines. J Label Compd Radiopharm 51:423-29CrossRef
  18.Wissenbach DK, Meyer MR, Remane D, Weber AA, Maurer HH (2011) Development of the first metabolite-based LC–MSn urine drug screening procedure - exemplified for antidepressants. Anal Bioanal Chem 400:79-8CrossRef
  19.Meyer MR, Vollmar C, Schwaninger AE, Maurer HH (2012) New cathinone-derived designer drugs 3
  omomethcathinone and 3-fluoromethcathinone: studies on their metabolism in rat urine and human liver microsomes using GC–MS and LC-high-resolution MS and their detectability in urine. J Mass Spectrom 47:253-62CrossRef
  20.Helfer AG, Turcant A, Boels D, Ferec S, Lelievre B, Welter J, Meyer MR, Maurer HH (2015) Elucidation of the metabolites of the novel psychoactive substance 4-methyl-N-ethyl-cathinone (4-MEC) in human urine and pooled liver microsomes by GC–MS and LC–HR–MS–MS techniques and of its detectability by GC–MS or LC–MS n standard screening approaches. Drug Test Anal 7:368-75CrossRef
  21.Maurer HH, Pfleger K, Weber AA (2011) Mass spectral and GC data of drugs, poisons, pesticides, pollutants and their metabolites. Wiley-VCH, Weinheim (Germany)
  22.Welter J, Kavanagh P, Maurer HH (2014) GC–MS and LC-(high-resolution)-MS n studies on the metabolic fate and detectability of camfetamine in rat urine. Anal Bioanal Chem 406:3815-829CrossRef
  23.Maurer HH, Pfleger K, Weber AA (2015) Mass spectral library of drugs, poisons, pesticides, pollutants and their metabolites. Wiley-VCH, Weinheim
  24.Meyer MR, Peters FT, Maurer HH (2010) Automated mass spectral deconvolution and identification system for GC–MS screening for drugs, poisons, and metabolites in urine. Clin Chem 56:575-84CrossRef
  25.Maurer HH, Wisse
• 作者单位：Julian A. Michely (1)
  Andreas G. Helfer (1)
  Simon D. Brandt (2)
  Markus R. Meyer (1) (3)
  Hans H. Maurer (1)
  
  1. Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421, Homburg, Saar, Germany
  2. School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, L3 3AF, Liverpool, UK
  3. Farmakologiska laboratoriet, Klinisk farmakologi, Karolinska Universitetssjukhuset Huddinge, Karolinska Institutet, 141 86, Stockholm, Sweden
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Analytical Chemistry
  Food Science
  Inorganic Chemistry
  Physical Chemistry
  Monitoring, Environmental Analysis and Environmental Ecotoxicology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1618-2650

文摘

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. Keywords Designer drugs DALT 5-MeO-DALT Metabolism SUSA LC–HR–MS–MS