PMID- 22573603
OWN - NLM
STAT- MEDLINE
DCOM- 20131021
LR  - 20191210
IS  - 1942-7611 (Electronic)
IS  - 1942-7603 (Linking)
VI  - 5
IP  - 6
DP  - 2013 Jun
TI  - In vitro metabolism studies on mephedrone and analysis of forensic cases.
PG  - 430-8
LID - 10.1002/dta.1369 [doi]
AB  - The stimulant designer drug mephedrone is a derivative of cathinone - a monoamine 
      alkaloid found in khat - and its effect resembles that of 
      3,4-Methylenedioxymethamphetamine (MDMA). Abuse of mephedrone has been documented 
      since 2007; it was originally a 'legal high' drug, but it has now been banned in 
      most Western countries. Using cDNA-expressed CYP enzymes and human liver 
      microsomal preparations, we found that cytochrome P450 2D6 (CYP2D6) was the main 
      responsible enzyme for the in vitro Phase I metabolism of mephedrone, with some 
      minor contribution from other NAPDH-dependent enzymes. Hydroxytolyl-mephedrone 
      and nor-mephedrone were formed in vitro, and the former was purified and 
      identified by nuclear magnetic resonance (NMR). In four forensic traffic cases 
      where mephedrone was detected, we identified hydroxytolyl-mephedrone and 
      nor-mephedrone again; as well as 4-carboxy-dihydro-mephedrone, which has been 
      previously described; and two new metabolites: dihydro-mephedrone and 
      4-carboxy-mephedrone. Fragmentation patterns for all detected compounds were 
      determined by a UPLC-QTOF/MS(E) system, and a fragmentation pathway via a 
      conjugated indole structure was proposed for most of the metabolites. Blood 
      concentrations in the forensic traffic cases ranged from 1 to 51 microg/kg for 
      mephedrone, and from not detected to 9 microg/kg for hydroxytolyl-mephedrone. In one 
      case, urine concentrations were also determined to be 700 microg/kg for mephedrone 
      and 190 microg/kg for hydroxytolyl-mephedrone. All compounds were detected or 
      quantified with an ultra performance liquid chromatography-tandem mass 
      spectrometry (UPLC-MS/MS) system and an ultra performance liquid 
      chromatography-time of flight/mass spectrometry (UPLC-TOF/MS) system.
CI  - Copyright (c) 2012 John Wiley & Sons, Ltd.
FAU - Pedersen, Anders Just
AU  - Pedersen AJ
AD  - Department of Forensic Medicine, Faculty of Health Sciences, University of 
      Copenhagen, Denmark. anders.pedersen@forensic.ku.dk
FAU - Reitzel, Lotte Ask
AU  - Reitzel LA
FAU - Johansen, Sys Stybe
AU  - Johansen SS
FAU - Linnet, Kristian
AU  - Linnet K
LA  - eng
PT  - Journal Article
DEP - 20120509
PL  - England
TA  - Drug Test Anal
JT  - Drug testing and analysis
JID - 101483449
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Designer Drugs)
RN  - 0 (Illicit Drugs)
RN  - 44RAL3456C (Methamphetamine)
RN  - 8BA8T27317 (mephedrone)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
SB  - IM
MH  - Central Nervous System Stimulants/blood/*metabolism/urine
MH  - Chromatography, High Pressure Liquid
MH  - Cytochrome P-450 CYP2D6/metabolism
MH  - Designer Drugs/*metabolism/pharmacokinetics
MH  - Forensic Medicine
MH  - Humans
MH  - Illicit Drugs/blood/*metabolism/urine
MH  - Methamphetamine/*analogs & derivatives/blood/metabolism/urine
MH  - Microsomes, Liver/metabolism
MH  - Tandem Mass Spectrometry
EDAT- 2012/05/11 06:00
MHDA- 2013/10/22 06:00
CRDT- 2012/05/11 06:00
PHST- 2011/12/22 00:00 [received]
PHST- 2012/03/19 00:00 [revised]
PHST- 2012/04/10 00:00 [accepted]
PHST- 2012/05/11 06:00 [entrez]
PHST- 2012/05/11 06:00 [pubmed]
PHST- 2013/10/22 06:00 [medline]
AID - 10.1002/dta.1369 [doi]
PST - ppublish
SO  - Drug Test Anal. 2013 Jun;5(6):430-8. doi: 10.1002/dta.1369. Epub 2012 May 9.