Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms

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

doi:10.1007/s11419-014-0245-6

Cited by 81 publications

(72 citation statements)

References 16 publications

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“…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]. We also reported a fatal case due to the combined use of two synthetic cannabinoids, AB-CHMINACA and 5-fluoro-AMB, and the N-methyl-D-aspartate receptor channel blocker diphenidine [12].…”

Section: Introductionmentioning

confidence: 71%

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: Introductionmentioning

confidence: 71%

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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“…Hasegawa et al 16 also reported the post mortem distribution of MAB-CHMINACA. In this case report, MAB-CHMINACA was reported in the highest concentration in pericardial blood and whole blood specimens.…”

Section: Pharmacology and Toxicologymentioning

confidence: 94%

“…Data was collected between 4000/cm and 6000/cm with a resolution of 4/cm for 32 scans. The results were confirmed using GC-MS. 15 Hasegawa et al 16 was the first to state that the presence of AB-CHMINACA, 5F-fluoro-AMB and diphenidine were found in herbal incense (Super Lemon). This compound caused the death of a 30-yearold male.…”

Section: Uchiyama Et Almentioning

confidence: 99%

“…Using GC-MS and comparing it to the spectral library the total ion chromatogram (TIC) showed two distinct peaks, leading to the conclusion that one would be the SCs, and the other diphenidine after comparing mass spectral patterns to an established library. 16 The more information that is collected and maintained about these compounds allows for scientists and clinicians to know how to start investigations when new compounds may arise from the black market (Figure 1-12). …”

Section: Uchiyama Et Almentioning

confidence: 99%

“…Hasegawa et al 16 reported a fatal case of drug poisoning of a 30 year old man, who was found dead in his car, with herbal incense (Super Lemon) containing multiple compounds including AB-CHMINACA, 5F fluoro-AMB, and diphenidine. Samples for toxicology examinations were taken from femoral vein blood, heart blood, urine, and eight solid tissues including adipose tissue.…”

Section: Pharmacology and Toxicologymentioning

confidence: 99%

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How Present Synthetic Cannabinoids Can Help Predict Symptoms in the Future

Mozayani¹

2016

MOJT

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Abbreviations: SCs, synthetic cannabinoids; Δ-9-THC, delta-9-tetrahydracannabinol; UHPLC, ultra high performance liquid chromatography; DAD, photodiode array; MS, mass spectrometry; GC, gas chromatography; DART, direct analysis in real time; TOF, time of flight spectrometry; NMR, nuclear magnetic resonance; ATR, attenuated total resonance; FTIR, fourier transform infrared spectrometry; TIC, total ion chromatogram; LC-MS/MS, liquid chromatography tandem mass spectrometry; CNS, central nervous system; LOD, limit of detection; LOQ, limit of quantitation; ULOL, upper limit of linearity; DUID, driving under the influence of drug; HLM, human liver microsomes; HPM, human pulmonary microsomes; CES 1, carboxylesterase 1 IntroductionSynthetic cannabinoids (SCs) are synthetic compounds sprayed on herbal products and have spread worldwide since 2004. Many of these compounds, more specifically l-valinamides and l-tert-leucinamides, are often characterized as part of the third, fourth and fifth generation of synthetic cannabinoids. There are many street names for herbal like compounds which are sprayed with these compounds, referred to as "Spice" such as Spice Diamond, Spice Gold, Spice Arctic Energy, Magic, Voodoo and Yucatan Fire. Such drugs are easily obtainable via the Internet, in smoke shops, and street markets. To evade law enforcement, these herbal incense products are often labeled "not for human consumption". Despite this, many countries have entered many synthetic cannabinoids to schedule 1. 1,2Initial reports of synthetic cannabinoids (SCs) in Unites States were in November 2008. In December 2008, German forensic laboratories initially identified JWH-018 and cannabicyclohexanol (CP-47,497 C8 homologue). The synthetic cannabinoids are frequently applied on plant material and inhaled. In January 2010, the popularity of these cannabinoids and their associated products appeared to have increased in the United States.3 Numerous SCs have been identified as adulterants, which have been seized by law enforcement. JWH-018, JWH-073, JWH-200, CP-47,497, and CP-47,497 C8 homologues were the first SCs identified as being abused. New generations of synthetic cannabinoids quickly emerged to evade law enforcement. After various laws were passed in the United States, different generations of SCs emerged varying only by slight modifications in structure. Some recent SCs include AB-CHMINACA and AB-PINACA. These substances are commonly marketed under the guise of being a ''legal high'' with a disclaimer of ''not for human consumption''. Law enforcement, public health officials, and clinicians are encountering cases in which there has been abuse of these substances, 4 requiring up to date information of the drug legislation, chemistry of the compounds and their detection, as well as the toxicology to be able to help identify these compounds when they present clinically.After the passage of the Synthetic Drug Abuse Prevent Act of 2012 in the United States, a third and fourth generation of SCs including UR-144, XLR11, and AKB-48 emerged...

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In vitro and in vivo human metabolism of the synthetic cannabinoid AB‐CHMINACA

Erratico

Negreira

Norouzizadeh

et al. 2015

Drug Testing and Analysis

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N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide (AB-CHMINACA) is a recently introduced synthetic cannabinoid. At present, no information is available about in vitro or in vivo human metabolism of AB-CHMINACA. Therefore, biomonitoring studies to screen AB-CHMINACA consumption lack any information about the potential biomarkers (e.g. metabolites) to target. To bridge this gap, we investigated the in vitro metabolism of AB-CHMINACA using human liver microsomes (HLMs). Formation of AB-CHMINACA metabolites was monitored using liquid chromatography coupled to time-of-flight mass spectrometry. Twenty-six metabolites of AB-CHMINACA were detected including seven mono-hydroxylated and six di-hydroxylated metabolites and a metabolite resulting from N-dealkylation of AB-CHMINACA, all produced by cytochrome P450 (CYP) enzymes. Two carboxylated metabolites, likely produced by amidase enzymes, and five glucuronidated metabolites were also formed. Five mono-hydroxylated and one carboxylated metabolite were likely the major metabolites detected. The involvement of individual CYPs in the formation of AB-CHMINACA metabolites was tested using a panel of seven human recombinant CYPs (rCYPs). All the hydroxylated AB-CHMINACA metabolites produced by HLMs were also produced by the rCYPs tested, among which rCYP3A4 was the most active enzyme. Most of the in vitro metabolites of AB-CHMINACA were also present in urine obtained from an AB-CHMINACA user, therefore showing the reliability of the results obtained using the in vitro metabolism experiments conducted to predict AB-CHMINACA in vivo metabolism. The AB-CHMINACA metabolites to target in biomonitoring studies using urine samples are now reliably identified and can be used for routine analysis.

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Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms

Cited by 81 publications

References 16 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

How Present Synthetic Cannabinoids Can Help Predict Symptoms in the Future

In vitro and in vivo human metabolism of the synthetic cannabinoid AB‐CHMINACA

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