PMID- 21980168
OWN - NLM
STAT- MEDLINE
DCOM- 20120120
LR  - 20211020
IS  - 1530-8561 (Electronic)
IS  - 0009-9147 (Print)
IS  - 0009-9147 (Linking)
VI  - 57
IP  - 12
DP  - 2011 Dec
TI  - Urinary excretion kinetics of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) 
      and its phase I and phase II metabolites in humans following controlled MDMA 
      administration.
PG  - 1748-56
LID - 10.1373/clinchem.2011.172254 [doi]
AB  - 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.
FAU - Schwaninger, Andrea E
AU  - Schwaninger AE
AD  - Department of Experimental and Clinical Toxicology, Institute of Experimental and 
      Clinical Pharmacology and Toxicology, Saarland University, Homburg (Saar), 
      Germany.
FAU - Meyer, Markus R
AU  - Meyer MR
FAU - Barnes, Allan J
AU  - Barnes AJ
FAU - Kolbrich-Spargo, Erin A
AU  - Kolbrich-Spargo EA
FAU - Gorelick, David A
AU  - Gorelick DA
FAU - Goodwin, Robert S
AU  - Goodwin RS
FAU - Huestis, Marilyn A
AU  - Huestis MA
FAU - Maurer, Hans H
AU  - Maurer HH
LA  - eng
GR  - ZIA DA000468-07/Intramural NIH HHS/United States
GR  - ZIA DA000468-08/Intramural NIH HHS/United States
GR  - ZIA DA000468-09/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111006
PL  - England
TA  - Clin Chem
JT  - Clinical chemistry
JID - 9421549
RN  - 0 (Glucuronides)
RN  - 0 (Sulfuric Acid Esters)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Administration, Oral
MH  - Double-Blind Method
MH  - Glucuronides/urine
MH  - Humans
MH  - Metabolic Detoxication, Phase I
MH  - Metabolic Detoxication, Phase II
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & 
      dosage/pharmacokinetics/*urine
MH  - Sulfuric Acid Esters/urine
PMC - PMC3717351
MID - NIHMS487012
COIS- Authors' Disclosures or Potential Conflicts of Interest: Upon manuscript 
      submission, all authors completed the Disclosures of Potential Conflict of 
      Interest form. Potential conflicts of interest: Employment or Leadership: None 
      declared. Consultant or Advisory Role: None declared. Stock Ownership: None 
      declared. Honoraria: None declared. Expert Testimony: None declared.
EDAT- 2011/10/08 06:00
MHDA- 2012/01/21 06:00
PMCR- 2013/07/21
CRDT- 2011/10/08 06:00
PHST- 2011/10/08 06:00 [entrez]
PHST- 2011/10/08 06:00 [pubmed]
PHST- 2012/01/21 06:00 [medline]
PHST- 2013/07/21 00:00 [pmc-release]
AID - clinchem.2011.172254 [pii]
AID - 10.1373/clinchem.2011.172254 [doi]
PST - ppublish
SO  - Clin Chem. 2011 Dec;57(12):1748-56. doi: 10.1373/clinchem.2011.172254. Epub 2011 
      Oct 6.