Postmortem Tissue Distribution of MDPV Following Lethal Intoxication by "Bath Salts"

Abstract

3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive, synthetic analog of the central nervous system stimulant cathinone. Its recent popularity as a recreational drug in the United States has led to numerous reports to poison control centers across the country. As with other synthetic cathinones, the recreational use of MDPV has resulted in death. MDPV is thought to exert its pharmacologic effects by inhibiting the reuptake of dopamine and norepinephrine. This report describes the case of an exposure of a 39-year-old male to MDPV, which resulted in his death. Postmortem concentrations of MDPV in various tissues were measured. The detection of MDPV in tissues and fluids was accomplished using gas chromatography-mass spectrometry analysis after solid-phase extraction. Blood analysis also demonstrated therapeutic levels of lamotrigine, fluoxetine, risperidone, benztropine, pseudoephedrine and ibuprofen. The detection of cathinones in hair was conducted using high-performance liquid chromatography-tandem mass spectrometry after solid-phase extraction. MDPV was uniformly distributed among multiple tissues (blood, brain, muscle, cerebrospinal fluid and lung) at concentrations of approximately 0.4 to 0.6 µg/mL. Tissue and fluids responsible for detoxification/excretion had higher concentrations of MDPV (kidney, liver and bile > 0.8 µg/mL). A blood concentration ≥ 0.4 µg/mL was judged sufficient to cause death. The cause of death was ruled MDPV intoxication resulting in cardiac arrhythmia.

In vitro Phase I and Phase II metabolism of α-pyrrolidinovalerophenone (α-PVP), methylenedioxypyrovalerone (MDPV) and methedrone by human liver microsomes and human liver cytosol

“…In Electronic supplementary material The online version of this article (doi:10.1007/s00216-015-8763-6) contains supplementary material, which is available to authorized users. spite of their recent introduction, deaths associated with the use of these NPS were already reported [13][14][15][16][17][18].…”

Quantification of Synthetic Cathinones in Rat Brain Using HILIC–ESI-MS/MS

“…As the chemistry of these compounds is constantly evolving, some investigators have taken a qualitative or semi-quantitative/screening approach to their analysis using gas chromatography-mass spectrometry (GC-MS) to measure several cathinones in a single sample (2,14). Using GC-MS, MDPV has been measured in blood (15)(16)(17), tissue (18), and urine (17)(18)(19)(20). Mephedrone has been quantified in blood and urine (21) while methylone has been analyzed in blood samples (22).…”

“…Most of these involved quantification from blood, plasma, or urine, and the majority utilized protein precipitation (PP) or liquid-liquid extraction (LLE) as the means of sample preparation (26). For example, Adamowizc et al achieved a 0.08 ng/mL LOD for mephedrone in post-mortem blood prepared by PP (27), and LLE was used to prepare cathinone-containing samples for LC-MS of urine (20,28,29), plasma (30), blood (1,28,29,31), and hair (16,18). Additionally, PP was used to prepare blood samples for a more general screening assay of nine synthetic cathinones (32).…”

“…Additionally, PP was used to prepare blood samples for a more general screening assay of nine synthetic cathinones (32). Assays for quantification of cathinones from tissues are limited (18,33). To date, quantification of synthetic cathinones in brain tissue has only been published for MDPV in the context of a single case report (18), yet brain a vital matrix for understanding these compounds' access to pharmacologic targets.…”

“…Assays for quantification of cathinones from tissues are limited (18,33). To date, quantification of synthetic cathinones in brain tissue has only been published for MDPV in the context of a single case report (18), yet brain a vital matrix for understanding these compounds' access to pharmacologic targets. As such, the purpose of this study was to develop a quantitative assay for MDPV, mephedrone, and methylone, in rat brain tissue for application toward a pharmacokinetic investigation of these drugs' behavior following intraperitoneal administration.…”