title: Urinary excretion kinetics of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and its phase I and phase II metabolites in humans following controlled MDMA administration.
abstract: BACKGROUND
  3,4-Methylendioxymethamphetamine (MDMA) is excreted inhuman urine as unchanged drug and phase I and II metabolites. Previous urinary excretion studies after controlled oral MDMA administration have been performed only after conjugate cleavage. Therefore, we investigated intact MDMA glucuronide and sulfate metabolite excretion.
  
  
  METHODS
  We used LC-high-resolution MS and GC-MS to reanalyze blind urine samples from 10 participants receiving 1.0 or 1.6 mg/kg MDMA orally. We determined median C(max),t(max), first and last detection times, and total urinary recovery; calculated ratios of sulfates and glucuronides; and performed in vitro-in vivo correlations.
  
  
  RESULTS
  Phase II metabolites of 3,4-dihydroxymethamphetamine (DHMA),4-hydroxy-3-methoxymethamphetamine (HMMA),3,4-dihydroxyamphetamine (DHA), and 4-hydroxy-3-methoxyamphetamine were identified, although only DHMA sulfates, HMMA sulfate, and HMMA glucuronide had substantial abundance. Good correlation was observed for HMMA measured after acid hydrolysis and the sum of unconjugated HMMA, HMMA glucuronide, and HMMA sulfate (R(2) = 0.87). More than 90% of total DHMA and HMMA were excreted as conjugates. The analyte with the longest detection time was HMMA sulfate. Median HMMA sulfate/glucuronide and DHMA 3-sulfate/4-sulfate ratios for the first 24 h were 2.0 and 5.3, respectively, in accordance with previous in vitro calculations from human liver microsomes and cytosol experiments.
  
  
  CONCLUSIONS
  Human MDMA urinary metabolites are primarily sulfates and glucuronides,with sulfates present in higher concentrations than glucuronides. This new knowledge may lead to improvements in urine MDMA and metabolite analysis in clinical and forensic toxicology, particularly for the performance of direct urine analysis.
authors: Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, Homburg (Saar), Germany.
authors: Andrea E
authors: AE
authors: Schwaninger
authors: Markus R
authors: MR
authors: Meyer
authors: Allan J
authors: AJ
authors: Barnes
authors: Erin A
authors: EA
authors: Kolbrich-Spargo
authors: David A
authors: DA
authors: Gorelick
authors: Robert S
authors: RS
authors: Goodwin
authors: Marilyn A
authors: MA
authors: Huestis
authors: Hans H
authors: HH
authors: Maurer
mesh_terms: D000284:Administration, Oral; D004311:Double-Blind Method; D020719:Glucuronides / Q000652:urine; D006801:Humans; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine*; D013463:Sulfuric Acid Esters / Q000652:urine
chemical_list: D020719:Glucuronides; D013463:Sulfuric Acid Esters; D018817:N-Methyl-3,4-methylenedioxyamphetamine