3,4-Methylenedioxypyrovalerone (MDPV) and metabolites quantification in human and rat plasma by liquid chromatography-high resolution mass spectrometry.
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 μL human and rat plasma. Plasma hydrolysis was followed by protein precipitation before analysis. Limits of detection were 0.1 μg L(-1), with linear ranges from 0.25 to 1000 μg 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 °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 μg L(-1) prior to and up to 8h after dosing. This method provides a simultaneous quantification of MDPV and two metabolites in plasma with good selectivity and sensitivity.
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
Sebastien
S
Anizan
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA; Program in Toxicology, University of Maryland Baltimore, Baltimore, MD, USA.
Kayla
K
Ellefsen
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
Marta
M
Concheiro
Drug Design and Synthesis Section, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Baltimore, MD, USA; On leave from the Medicinal Chemistry Group, Qs' Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
Masaki
M
Suzuki
Drug Design and Synthesis Section, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Baltimore, MD, USA.
Kenner C
KC
Rice
Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
Michael H
MH
Baumann
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA. Electronic address: mhuestis@intra.nida.nih.gov.
Marilyn A
MA
Huestis
D000818:Animals; D052117:Benzodioxoles / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D001774:Blood Chemical Analysis / Q000379:methods*; D002853:Chromatography, Liquid; D006801:Humans; D006868:Hydrolysis; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry; D011759:Pyrrolidines / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D015203:Reproducibility of Results; D000094982:Synthetic Cathinone
D052117:Benzodioxoles; D011759:Pyrrolidines; D000094982:Synthetic Cathinone
HRMS; LC–MS/MS; MDPV; Metabolites; Synthetic cathinones