Postmortem distribution of α-pyrrolidinobutiophenone in body fluids and solid tissues of a human cadaver

Wurita, Amin; Hasegawa, Koutaro; Minakata, Kumagusu; Gonmori, Kunio; Nozawa, Hideki; Yamagishi, Itaru; Сузукі, Осаму; Watanabe, Kota

doi:10.1016/j.legalmed.2014.05.001

Cited by 56 publications

(34 citation statements)

References 13 publications

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“…The standard addition method seems to be the best choice in particular for comparison of concentrations in matrices with fairly different properties, and this method was employed in the current study. The details of the procedure and calculation of the results have been detailed in our previous reports [8,17].…”

Section: Standard Addition Methodsmentioning

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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Section: Standard Addition Methodsmentioning

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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“…In this study, because we were dealing with three herbal blends, all with properties that were likely quite different, we also used the standard addition method, although each acetonitrile extract solution was highly diluted. The principle of the method and examples of the standard addition calibration curve were discussed in detail in our previous report [15].…”

Section: Standard Addition Methodsmentioning

confidence: 99%

Identification and quantitation of 5-fluoro-ADB-PINACA and MAB-CHMINACA in dubious herbal products

et al. 2015

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Police officials brought three different packages of herbal blends, with brand names ''AL 37'', ''AP 31'', and ''GM sapphire'', to our laboratory for drug testing. Using our in-house high-resolution mass spectrometric analysis, we were able to estimate the presence of 5-fluoro-ADB-PINACA and MAB-CHMINACA in them without their reference standards. After obtaining the reference standards, we compared the mass spectra of the extracts of the herbal blends with those of the reference standards using both gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. The mass spectra of the herbal blend extracts coincided with those of the reference standards, disclosing the presence of 5-fluoro-ADB-PINACA in ''AL 37'' and ''AP 31'', and MAB-CHMINACA in ''GM sapphire''. We then quantitated the concentrations of both compounds in the herbal blends using the standard addition method. The concentrations of 5-fluoro-ADB-PINACA were 19.4 ± 0.55 and 19.0 ± 0.47 mg/g (mean ± standard deviation of triplicate determinations) for herbal product brands ''AL 37'' and ''AP 31'', respectively, and that of MAB-CHMINACA was 133 ± 4.5 mg/g for the ''GM sapphire'' herbal product. To our knowledge, this is the first study to demonstrate the identification and quantitation of the newest synthetic cannabinoids 5-fluoro-ADB-PINACA and MAB-CHMIN-ACA in herbal blend products.

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“…In addition, the method requires no blank human specimens that are negative for a target compound; generally, the collection of nonessential human tissue sample should be avoided because of ethical reasons. The principle and the calculation method of the standard addition method are described in our previous report [3,7,11].…”

Section: Standard Addition Methodsmentioning

confidence: 99%

“…The highest concentration of PV9 was observed for the kidney, followed by the skeletal muscle, pancreas, adipose tissue, liver, lung, spleen, heart muscle, and brain. In our previous reports [3,11], we reported the postmortem distribution of a-pyrrolidinovalerophenone (a-PVP) and apyrrolidinobutiophenone (a-PBP) in body fluids and solid tissues of human cadavers. PV9, a-PVP, and a-PBP are all a-pyrrolidinophenone derivative analogs.…”

Section: Identification Of Pv9 By Lc-ms-msmentioning

confidence: 99%

Postmortem distribution of PV9, a new cathinone derivative, in human solid tissues in a fatal poisoning case

et al. 2014

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In our previous study, we identified PV9 [1-phenyl-2-(pyrrolidin-1-yl)octan-1-one] in human blood and urine in a fatal poisoning case. The victim was an 18-yearold woman. After ingesting ''aroma liquid'' solution, the victim showed various symptoms including low levels of consciousness, and was taken to a hospital emergency department. Although the victim received intensive medical treatment including an intravenous drip infusion of a large volume of transfusion solution, she was pronounced dead about 20 h after admission. In this study, we carefully examined the postmortem distribution of PV9 in nine solid tissues of the victim collected at forensic autopsy. The extraction of PV9 and internal standard (IS) PV8 [1-phenyl-2-(1-pyrrolidinyl)-1-heptanone] was performed by acetonitrile deproteinization, followed by modified QuEChERS dispersive solid-phase extraction and filtration through Captiva ND Lipids cartridges. Anaysis was performed by liquid chromatography-tandem mass spectrometry. Because this study dealt with various kinds of human matrices, we used the standard addition method to overcome matrix effects. After thorough validations, such as checking the product ion mass spectra, selected reaction monitoring chromatograms, linearity of the standard addition calibration curves, the intraday and interday repeatability, matrix effects, and recovery rates for the method, the concentrations of PV9 in nine solid tissue specimens were measured using PV8 as IS. The highest level of PV9 was found in the kidney at 907 ± 19.5 ng/g followed by the skeletal muscle, pancreas, adipose tissue, liver, lung, spleen, heart muscle, and brain. The lowest level of PV9 in the brain was 212 ± 11.9 ng/g. The high level of PV9 in the kidney suggests that this drug tends to be rapidly excreted into urine via the kidney as was the case for apyrrolidinovalerophenone. The low concentration of PV9 in the brain was unexpected, because this drug is a psychotropic drug with a long hydrophobic side chain, and is considered to cross the blood-brain barrier very easily. To our knowledge, this is the first demonstration of the distribution of the new pyrrolidinophenone derivative PV9 in human solid tissues in a poisoning case.Keywords PV9 Á a-POP Á 1-Phenyl-2-(pyrrolidin-1-yl)octan-1-one Á Cathinone derivative Á Distribution in human organs Á LC-MS-MS

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Postmortem distribution of α-pyrrolidinobutiophenone in body fluids and solid tissues of a human cadaver

Cited by 56 publications

References 13 publications

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

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

Identification and quantitation of 5-fluoro-ADB-PINACA and MAB-CHMINACA in dubious herbal products

Postmortem distribution of PV9, a new cathinone derivative, in human solid tissues in a fatal poisoning case

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