A fatal case of 3,4-methylenedioxypyrovalerone poisoning: coexistence of α-pyrrolidinobutiophenone and α-pyrrolidinovalerophenone in blood and/or hair

Namera, Akira; Urabe, Shumari; Saito, Takeshi; Torikoshi-Hatano, Aiko; Shiraishi, Hiroaki; Arima, Yasunobu; Nagao, Masataka

doi:10.1007/s11419-013-0192-7

Cited by 63 publications

(45 citation statements)

References 24 publications

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“…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].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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The aim of the present study was to identify the in vitro Phase I and Phase II metabolites of three new psychoactive substances: α-pyrrolidinovalerophenone (α-PVP), methylenedioxypyrovalerone (MDPV), and methedrone, using human liver microsomes and human liver cytosol. Accurate-mass spectra of metabolites were obtained using liquid chromatography-quadrupole time-of-flight mass spectrometry. Six Phase I metabolites of α-PVP were identified, which were formed involving reduction, hydroxylation, and pyrrolidine ring opening reactions. The lactam compound was the major metabolite observed for α-PVP. Two glucuronidated metabolites of α-PVP, not reported in previous in vitro studies, were further identified. MDPV was transformed into 10 Phase I metabolites involving reduction, hydroxylation, and loss of the pyrrolidine ring. Also, six glucuronidated and two sulphated metabolites were detected. The major metabolite of MDPV was the catechol metabolite. Methedrone was transformed into five Phase I metabolites, involving N- and O-demethylation, hydroxylation, and reduction of the ketone group. Three metabolites of methedrone are reported for the first time. In addition, the contribution of individual human CYP enzymes in the formation of the detected metabolites was investigated.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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“…In recent years, synthetic cannabinoids [1][2][3][4][5] and cathinones [6][7][8][9] have become widely distributed, and are now causing social problems throughout many parts of the world. Although the traditional marijuana and hashish containing D 9 -tetrahydrocannabinol as the psychoactive compound have been associated with almost no fatalities thus far, two reports have described fatalities caused by the synthetic cannabinoids MAM-2201 [10] and NNEI [11].…”

Section: Introductionmentioning

confidence: 99%

Identification and quantitation of 5-fluoro-ADB, one of the most dangerous synthetic cannabinoids, in the stomach contents and solid tissues of a human cadaver and in some herbal products

et al. 2014

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Since late September 2014, there have been approximately 10 cases in Japan where people have died from inhaling smoke from herbal blends containing a newly emerged synthetic cannabinoid. Although the drug was tentatively identified by some drug-monitoring institutions as 5-fluoro-ADB, to our knowledge, its data have not been published in any scientific context. We recently encountered an autopsy case in which 5-fluoro-ADB was involved. The deceased was a 34-year-old man who was found dead in his room. The postmortem interval was estimated at 35-40 h. The direct cause of the death was asphyxia due to aspiration of stomach contents into the trachea, which likely took place during vomiting under low-consciousness conditions provoked by inhalation of the 5-fluoro-ADB smoke. The cadaver was subjected to autopsy at our department. Femoral vein blood, right heart blood, left heart blood, urine, stomach contents, and nine solid tissues including the adipose tissue were collected and frozen until analysis. The extraction of 5-fluoro-ADB and internal standard 5-fluoro-AMB was performed using a modified QuEChERS method plus filtration through Captiva ND Lipids cartridges, followed by liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. Because this study dealt with various kinds of human matrices, we used the standard addition method for quantitation to overcome the matrix effects. The levels of 5-fluoro-ADB in the cadaver specimens were generally low; it could not be detected from blood or urine specimens. The levels of 5-fluoro-ADB in solid tissues were 1.17-7.95 ng/g. Because the highest levels were found for the adipose tissue and heart muscle, the final extracts of the adipose tissue and/or heart muscle were concentrated 10-and 200-fold to obtain product ion mass spectra of 5-fluoro-ADB using LC-MS-MS and its mass spectrum by gas chromatography-mass spectrometry, respectively. Both spectra completely coincided with those obtained from the reference standard 5-fluoro-ADB, confirming that the target compound was 5-fluoro-ADB. The quantitative results obtained by selected reaction monitoring of LC-MS-MS showed the highest level, at 7.95 ng/g, in the adipose tissue, followed by stomach contents, brain, heart muscle, pancreas, and spleen. For the lung, liver, kidney, and skeletal muscle, levels were below the quantitation limit (about 0.5 ng/g), although very small peaks above the detection limit (about 0.1 ng/g) could be observed for all of the above solid tissues. The low levels of 5-fluoro-ADB in the solid tissues were likely as a result of only a small amount of 5-fluoro-ADB incorporated into the body via the lungs due to the short period from the beginning of smoking the herb to the fatal asphyxia resulting from aspiration of a massive amount of stomach contents into the trachea under low-consciousness conditions. In addition, we measured the content of 5-fluoro-ADB in three packages, all of which were opened, that were found under a pillow near the deceased; their levels of 5-fluoro-ADB were 49.2 mg/g, ...

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“…Additionally, internal standard stock solutions were added at the following concentrations: 1 ng/mL D 8 -MDPV, 2 ng/mL D 3 -mephedrone, and 10 ng/mL D 3 -methylone. All brain tissue homogenate samples were vortexed and centrifuged (5 min; 1,500 rpm), and then supernatants were collected and subjected to SPE (16). SPE was performed using Clean Screen DAU extraction columns (UCT, Bristol, PA, USA).…”

Section: Specimen Preparationmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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The abuse of synthetic cathinones, formerly marketed as "bath salts", has emerged over the last decade. Three common drugs in this class include 3,4-methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4-methylenedioxymethcathinone (methylone). An LC-MS/MS method has been developed and validated for the simultaneous quantification of MDPV, mephedrone, and methylone in brain tissue. Briefly, MDPV, mephedrone, methylone, and their deuterium-labeled analogs were subjected to solid phase extraction (SPE) and separated using an HILIC Silica Column. The HPLC was coupled to a Shimadzu IT-TOF (ion trap-time of flight) system with the electrospray source running in positive mode (+ESI). The method was validated for precision, accuracy, and extraction efficiency. All inter-day and intra-day % RSD (percent relative standard deviation) and % error values were less than 15% and extraction efficiency exceeded 80%. These conditions allowed for limits of detection of 1ng/mL for MDPV, and 5 ng/mL for both mephedrone and methylone. The limits of quantification were determined to be 5ng/mL for MDPV and 10 ng/mL for mephedrone and methylone. The method was utilized to evaluate the pharmacokinetics of these drugs in adult male rats following administration of a drug cocktail including MDPV, mephedrone, and methylone. All three compounds reached peak concentrations in the brain within 15 min. Although methylone and mephedrone were administered at the same dose, the peak concentration (C max ) of mephedrone in the brain was significantly higher than that for methylone, as was the area under the curve (AUC). In summary, this quick and sensitive method for measuring synthetic cathinones may be used for future pharmacokinetic investigations of these drugs in target tissue.

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A fatal case of 3,4-methylenedioxypyrovalerone poisoning: coexistence of α-pyrrolidinobutiophenone and α-pyrrolidinovalerophenone in blood and/or hair

Cited by 63 publications

References 24 publications

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

Identification and quantitation of 5-fluoro-ADB, one of the most dangerous synthetic cannabinoids, in the stomach contents and solid tissues of a human cadaver and in some herbal products

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

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