PMID- 24682111
OWN - NLM
STAT- MEDLINE
DCOM- 20150130
LR  - 20211021
IS  - 1945-2403 (Electronic)
IS  - 0146-4760 (Print)
IS  - 0146-4760 (Linking)
VI  - 38
IP  - 5
DP  - 2014 Jun
TI  - In vitro metabolism of 3,4-methylenedioxymethamphetamine in human hepatocytes.
PG  - 249-55
LID - 10.1093/jat/bku023 [doi]
AB  - Users of the illicit drug, 3,4-methylenedioxymethamphetamine (MDMA), show signs 
      of neurotoxicity. However, the precise mechanism of neurotoxicity caused by use 
      of MDMA has not yet been elucidated. Synthetic glutathione (GSH) conjugates of 
      MDMA are transported into the brain by the GSH transporter and subsequently 
      produce neurotoxicity. The objective of this research is to show direct evidence 
      of the formation of GSH adducts of MDMA in human hepatocytes. High-performance 
      liquid chromatography coupled with tandem mass spectrometry was utilized to 
      examine in vitro incubations of MDMA with cryopreserved human hepatocytes. The 
      use of hydrophilic liquid chromatography in combination with linear ion trap mass 
      spectrometry permitted the identification of two possible GSH metabolites. 
      Enhanced product ion scans of m/z = 499 and 487 amu of extracts from hepatocytes 
      treated with 1.0 mM MDMA show a distinct fragmentation pattern (m/z 194.2, 163, 
      135, 105), suggesting the formation of MDMA-GSH conjugate, MDMA-SG and 
      3,4-dihydroxymethamphetamine-SG. The formation of an MDMA-GSH conjugate was 
      further supported by the apparent lack of the same fragmentation pattern from 
      hepatocyte samples without MDMA treatment. The results generated from this study 
      yield valuable qualitative and quantitative information about the neurotoxic 
      thioether metabolites formed from MDMA in humans.
FAU - Ramaley, Corinne
AU  - Ramaley C
AD  - 1Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, 
      Kittrell Hall, Hampton, VA 23668, USA.
FAU - Leonard, Susan C
AU  - Leonard SC
FAU - Miller, Jeffrey D
AU  - Miller JD
FAU - Wilson, Denita Takesha-Mashia
AU  - Wilson DT
FAU - Chang, Sai Y
AU  - Chang SY
FAU - Chen, Qingyu
AU  - Chen Q
FAU - Li, Feng
AU  - Li F
FAU - Du, Chengan
AU  - Du C
LA  - eng
GR  - 1R24DA012546-1/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140328
PL  - England
TA  - J Anal Toxicol
JT  - Journal of analytical toxicology
JID - 7705085
RN  - GAN16C9B8O (Glutathione)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Cells, Cultured
MH  - Chromatography, High Pressure Liquid
MH  - Glutathione/metabolism
MH  - Hepatocytes/*metabolism
MH  - Humans
MH  - Mass Spectrometry
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*metabolism
PMC - PMC4014114
EDAT- 2014/04/01 06:00
MHDA- 2015/01/31 06:00
PMCR- 2015/06/01
CRDT- 2014/04/01 06:00
PHST- 2014/04/01 06:00 [entrez]
PHST- 2014/04/01 06:00 [pubmed]
PHST- 2015/01/31 06:00 [medline]
PHST- 2015/06/01 00:00 [pmc-release]
AID - bku023 [pii]
AID - 10.1093/jat/bku023 [doi]
PST - ppublish
SO  - J Anal Toxicol. 2014 Jun;38(5):249-55. doi: 10.1093/jat/bku023. Epub 2014 Mar 28.