Journal
ANALYTICA CHIMICA ACTA
Volume 827, Issue -, Pages 54-63Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.aca.2014.04.015
Keywords
MDPV; Synthetic cathinones; LC-MS/MS; HRMS; Metabolites
Categories
Funding
- Intramural Research Program of the National Institute on Drug Abuse (NIDA)
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- National Institutes of Health (NIH)
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Synthetic cathinones are recreational drugs that mimic the effects of illicit stimulants like cocaine, amphetamine or Ecstasy. Among the available synthetic cathinones in the United States, 3,4-methylenedioxypyrovalerone (MDPV) is commonly abused and associated with dangerous side effects. MDPV is a dopamine transporter blocker 10-fold more potent than cocaine as a locomotor stimulant in rats. Previous in vitro and in vivo studies examining MDPV metabolism reported 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV) as the two primary metabolites. We developed and validated a liquid chromatography-high resolution mass spectrometry method to quantify MDPV and its primary metabolites in 100 mu L human and rat plasma. Plasma hydrolysis was followed by protein precipitation before analysis. Limits of detection were 0.1 mu g L (1), with linear ranges from 0.25 to 1000 mu g L (1). Process efficiency, matrix effect, total imprecision (%CV) and accuracy (%target) were 36-93%, from -8 to 12%, 2.1 to 7.3% and 86 to 109%, respectively. MDPV and metabolites were stable at room temperature for 24 h, 4 degrees C for 72 h and after 3 freeze-thaw cycles with less than 10% variability. Human-rat plasma cross validation demonstrated that rat plasma could be accurately quantified against a human plasma calibration curve. As proof of this method, rat plasma specimens were analyzed after intraperitoneal and subcutaneous dosing with MDPV (0.5 mg kg (1)). MDPV, 3,4-catechol-PV and 4-OH-3-MeO-PV concentrations ranged from not detected to 107.5 mu g L (1) prior to and up to 8 h after dosing. This method provides a simultaneous quantification of MDPV and two metabolites in plasma with good selectivity and sensitivity. Published by Elsevier B.V.
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