Assessing the toxicological significance of new psychoactive substances in fatalities

Elliott, Simon; Sedefov, Roumen; Evans-Brown, Michael

doi:10.1002/dta.2225

Cited by 41 publications

(25 citation statements)

References 35 publications

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“…Indeed, the interpretative weight assigned to SCs in cases of death can largely vary among different evaluators [27]. The lack of data regarding postmortem redistribution and toxic effects further represents a challenge when assessing the TSS [9] of SCs in death cases and highlights that concentrations should be interpreted with caution, in a multi-disciplinary evaluation including circumstantial data and morphological assessment [9,25].…”

Section: Discussionmentioning

confidence: 99%

“…Cases of deaths due or related to SCs are commonly reported in the literature, although the determination of the significance of toxicological results, as highlighted by Elliott et al [9], can be difficult and often lacks. The Toxicological Significance Score (TSS) is a system developed to perform and strengthen the health risk assessment of NPS and to allow the clarification of the role of such substance(s) in deaths.…”

Section: Introductionmentioning

confidence: 99%

“…Low, alternative cause of death) to 3 (i.e. High, NPS likely to have contributed to toxicity/death, despite the detection of other drugs) is assigned [9]. Six cases of death related to the intake of Cumyl-PEGACLONE were reported, in none of which, according to the TSS, the substance seemed to have played a causative role [8].…”

Section: Introductionmentioning

confidence: 99%

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Four cases of death involving the novel synthetic cannabinoid 5F-Cumyl-PEGACLONE

et al. 2019

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Purpose Cumyl-PEGACLONE was the first synthetic cannabinoid (SC) with a γ-carbolinone core structure detected in forensic casework and, since then, it has dominated the German SC-market. Here the first four cases of death involving its fluorinated analog, 5F-Cumyl-PEGACLONE, a recently emerged γ-carbolinone derived SC, are reported. Methods Complete postmortem examinations were performed. Postmortem samples were screened by immunoassay, gas chromatography mass spectrometry (GC-MS) or liquid chromatography tandem mass spectrometry. For quantification of SCs, the standard addition method was employed. Herbal blends were analyzed by GC-MS. In each case of death, the Toxicological Significance Score (TSS) was assigned to the compound. Results 5F-Cumyl-PEGACLONE was identified at concentrations ranging 0.09-0.45 ng/mL in postmortem femoral blood. In case 1, signs of hypothermia and kidney bleedings were noted. Despite a possible tolerance due to long term SC use, a TSS of 3 was assigned. In case 2, an acute heroin intoxication occurred and a contributory role (TSS = 1) of 5F-Cumyl-PEGACLONE was suggested. In case 3, a prisoner was found dead. GC-MS analysis of herbal blends, retrieved in his cell together with paraphernalia, confirmed the presence of 5F-Cumyl-PEGACLONE and a causative role was deemed probable (TSS = 2). In case 4, the aspiration of gastric content due to a SC-induced coma was observed (TSS = 3). Conclusions 5F-Cumyl-PEGACLONE is an emerging and extremely potent SC which raises serious public health concerns. A comprehensive analysis of circumstantial, clinical, and postmortem findings, as well as an in-depth toxicological analysis is necessary for a valid interpretation and for the assessment of the toxicological significance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Four cases of death involving the novel synthetic cannabinoid 5F-Cumyl-PEGACLONE

et al. 2019

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“…For case #18 no data was available. The assessment of the toxicological significance of the Cumyl‐PEGACLONE findings in analogy to Elliott et al led to a Toxicological Significance Score (TSS) of 1 (low, i.e., alternative cause of death) for three of these cases (#10, 11, and 13). A TSS of 2 (medium, i.e., Cumyl‐PEGACLONE may have contributed to death, but other findings may be more significant) could be assigned to the remaining two cases (#9 and 12).…”

Section: Fatal and Non‐fatal Intoxications Associated With The Consummentioning

confidence: 99%

Cumyl‐PEGACLONE: A comparatively safe new synthetic cannabinoid receptor agonist entering the NPS market?

Halter

Angerer

Röhrich

et al. 2018

Drug Testing and Analysis

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“…These results indicate that, for these substances, there is a potential use of the method developed for quantitative analysis after the evaluation of the other validation parameters, however considering that FMN values lower than 1 had the signal suppressed in the matrix presence and those with values greater than 1, increment. It is important to note, however, that there are often no defined concentration ranges associated with NPS that would correspond to degrees of toxicity and expected outcomes that indicates the likely role of a substance in contributing to or causing death (24). On the other hand, the substances not listed in Table 3 showed great variability in the FMN factors obtained, demonstrating the application of the method developed for their qualitative analysis only, since all met the criteria for positivity.…”

Section: Matrix Effectmentioning

confidence: 99%

Development and validation of a LC-ESI-MS/MS method for simultaneous whole blood analysis of 51 new psychoactive substances

2019

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In recent years, there has been a great increase in seizures and forensic analysis of new psychotropic substances (NPS) in the state of Rio Grande do Sul. The analysis of these compounds needs to be performed in biological samples in cases of violent deaths. A sensitive and reliable liquid chromatography-tandem mass spectrometry with electrospray ionization interface (LC-ESI-MS/MS) method was developed and validated for qualitative analysis of 51 NPS in whole blood forensic samples. Synthetic cathinones, phenethylamines, opioids, tryptamines, synthetic cannabinoids, and other hallucinogens and stimulants were included in the method. The validation parameters assessed were speciﬁcity, limit of detection, retention time precision, and matrix effect. Drug free pools (n=6) were used for validation, including post mortem samples as well as from living individuals. Adulterants, pharmaceuticals, metabolites, and other illicit drugs, totalling 39 compounds, were analyzed and no interference was noticed. The detection limits obtained were suitable for evaluation at recreational and non-fatal levels of consumption, mostly. The results revealed an appropriate matrix effect in 24 out of 51 substances tested, indicating the potential for future quantitative analysis with this method for these drugs. The developed and validated method is easy to implement, fast, with low cost, and suitable for use in routine forensic toxicology laboratory analysis.

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Assessing the toxicological significance of new psychoactive substances in fatalities

Cited by 41 publications

References 35 publications

Four cases of death involving the novel synthetic cannabinoid 5F-Cumyl-PEGACLONE

Four cases of death involving the novel synthetic cannabinoid 5F-Cumyl-PEGACLONE

Cumyl‐PEGACLONE: A comparatively safe new synthetic cannabinoid receptor agonist entering the NPS market?

Development and validation of a LC-ESI-MS/MS method for simultaneous whole blood analysis of 51 new psychoactive substances

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