In vitro metabolism studies on mephedrone and analysis of forensic cases. Issue 6 (9th May 2012)

• Record Type: Journal Article
• Authors: Pedersen, Anders Just; Reitzel, Lotte Ask; Johansen, Sys Stybe; Linnet, Kristian
• Is Part Of: Drug testing and analysis. Volume 5:Issue 6(2013:Jun.)
• Page Start: 430
• Page End: 438
• Publication Date: 2012-05-09
• Subjects: Drugs -- Analysis -- Periodicals; Drug testing -- Periodicals; Chemistry, Forensic -- Periodicals; 615.1901
• DOI: 10.1002/dta.1369
• Languages: English
• ISSNs: 1942-7603

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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.</p> <p>Using cDNA‐expressed CYP enzymes and human liver microsomal preparations, we found that cytochrome P450 2D6 (CYP2D6) was the main responsible enzyme for the <italic>in vitro</italic> Phase I metabolism of mephedrone, with some minor contribution from other NAPDH‐dependent enzymes.</p> <p>Hydroxytolyl‐mephedrone and nor‐mephedrone were formed <italic>in vitro</italic>, 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<sup>E</sup> 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 µg/kg for mephedrone, and from not detected to 9 µg/kg for hydroxytolyl‐mephedrone. In one case, urine concentrations were also determined to be 700 µg/kg for mephedrone and 190 µg/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. Copyright © 2012 John Wiley & Sons, Ltd.</p> </abstract>