PMID- 11559034
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20191210
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 14
IP  - 9
DP  - 2001 Sep
TI  - 3,4-Dihydroxymethamphetamine (HHMA). A major in vivo 
      3,4-methylenedioxymethamphetamine (MDMA) metabolite in humans.
PG  - 1203-8
AB  - There is evidence that some heavy users of 3,4-methylenedioxymethamphetamine 
      (MDMA, ecstasy) show signs of neurotoxicity (a cognitive dysfunction, a larger 
      incidence of psychopathology). It has been postulated that the catechol 
      intermediates of methylenedioxyamphetamines such as 3,4-dihydroxymethamphetamine 
      (HHMA), a metabolite of MDMA, may play a role in their neurotoxicity by formation 
      of thioether adducts. This study describes the first validated method for HHMA 
      determination in plasma and urine by strong cation-exchange solid-phase 
      extraction high-performance liquid chromatography/electrochemical detection 
      (HPLC/ED) analysis. The method has been applied for the determination of HHMA in 
      plasma and urine samples from a clinical study in healthy volunteers of MDMA and 
      provides preliminary kinetic data on this metabolite. HHMA appeared to be a major 
      MDMA metabolite with plasma concentrations as high as the parent compound. Thus, 
      HHMA C(max) (154.5 microg/L) and AUC(0-24h)(1990.9 microg/L h) were similar to 
      those obtained in previously published reports for MDMA (181.6 microg/L and 
      1465.9 microg/L h, respectively). The 24-h urinary recovery of HHMA accounted for 
      17.7% of the MDMA dose administered and increases the total 24 h recovery of MDMA 
      and metabolites to 58% of the 100 mg dose administered. The determination of HHMA 
      in plasma and urine samples is of interest in order to establish its relevance in 
      MDMA metabolism and its possible contribution to MDMA neurotoxicity in humans. 
      Its validation showed appropriate accuracy and precision for its use in 
      pharmacokinetic studies.
FAU - Segura, M
AU  - Segura M
AD  - Pharmacology Research Unit, Institut Municipal d'Investigacio Medica (IMIM), 
      Barcelona, Spain.
FAU - Ortuno, J
AU  - Ortuno J
FAU - Farre, M
AU  - Farre M
FAU - McLure, J A
AU  - McLure JA
FAU - Pujadas, M
AU  - Pujadas M
FAU - Pizarro, N
AU  - Pizarro N
FAU - Llebaria, A
AU  - Llebaria A
FAU - Joglar, J
AU  - Joglar J
FAU - Roset, P N
AU  - Roset PN
FAU - Segura, J
AU  - Segura J
FAU - de La Torre, R
AU  - de La Torre R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Hallucinogens)
RN  - 15398-87-5 (alpha-methylepinine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - R7339QLN1C (Deoxyepinephrine)
SB  - IM
MH  - Adult
MH  - Chromatography, High Pressure Liquid/methods
MH  - Deoxyepinephrine/*analogs & derivatives/*blood/*urine
MH  - Hallucinogens/*adverse effects/*metabolism
MH  - Humans
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*adverse effects/*metabolism
MH  - Sensitivity and Specificity
MH  - Toxicity Tests
EDAT- 2001/09/18 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/09/18 10:00
PHST- 2001/09/18 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/09/18 10:00 [entrez]
AID - tx010051p [pii]
AID - 10.1021/tx010051p [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2001 Sep;14(9):1203-8. doi: 10.1021/tx010051p.