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- Title
3,4-Methylenedioxymethamphetamine (MDMA) and metabolites disposition in blood and plasma following controlled oral administration.
- Authors
Hartman, Rebecca; Desrosiers, Nathalie; Barnes, Allan; Yun, Keming; Scheidweiler, Karl; Kolbrich-Spargo, Erin; Gorelick, David; Goodwin, Robert; Huestis, Marilyn
- Abstract
3,4-Methylenedioxymethamphetamine (MDMA) is an illicit phenethylamine ingested for entactogenic and euphoric effects. Although blood is more commonly submitted for forensic analysis, previous human MDMA pharmacokinetics research focused on plasma data; no direct blood-plasma comparisons were drawn. Blood and plasma specimens from 50 healthy adult volunteers (33 males, 17 females, 36 African-American) who ingested recreational 1.0 and 1.6 mg/kg MDMA doses were quantified for MDMA and metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-methylenedioxyamphetamine (MDA), and 4-hydroxy-3-methoxyamphetamine (HMA) by two-dimensional gas chromatography-mass spectrometry. Specimens were collected up to 3 h post-dose and evaluated for maximum concentration ( C), first detection time ( t), time of C ( t), and 3-h area under the curve (AUC); as well as blood metabolite ratios and blood/plasma ratios. Median blood MDMA and MDA C were significantly greater ( p < 0.0005) than in plasma, but HMMA was significantly less ( p < 0.0005). HMA was detected in few blood specimens, at low concentrations. Nonlinear pharmacokinetics were not observed for MDMA or MDA in this absorptive phase, but HMMA C and AUC were similar for both doses despite the 1.6-fold dose difference. Blood MDA/MDMA and MDA/HMMA significantly increased ( p < 0.0001) over the 3-h time course, and HMMA/MDMA significantly decreased ( p < 0.0001). Blood MDMA C was significantly greater in females ( p = 0.010) after the low dose only. Low-dose HMMA AUC was significantly decreased in females' blood and plasma ( p = 0.027) and in African-Americans' plasma ( p = 0.035). These data provide valuable insight into MDMA blood-plasma relationships for forensic interpretation and evidence of sex- and race-based differential metabolism and risk profiles. [Figure not available: see fulltext.]
- Subjects
ECSTASY (Drug); METABOLITES; BLOOD plasma; CONTROLLED release drugs; ORAL medication; PHARMACOKINETICS
- Publication
Analytical & Bioanalytical Chemistry, 2014, Vol 406, Issue 2, p587
- ISSN
1618-2642
- Publication type
Article
- DOI
10.1007/s00216-013-7468-y