Detection and quantification of 5F-ADB and its methyl ester hydrolysis metabolite in fatal intoxication cases by liquid chromatography–high resolution mass spectrometry

Yeter, Oya; Öztürk, Yeter Erol

doi:10.1016/j.forsciint.2019.06.024

Cited by 19 publications

(18 citation statements)

References 21 publications

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“…For instance, MDMB‐CHMICA was the most reported SC in Germany and Poland from 2013 to the first half of 2017 . 5F‐ADB was the most frequently detected SC in post‐mortem blood and urine samples in Turkey between 2017 and 2018 . JWH‐018 and XLR11 were consistently prevalent in the US between 2010 and 2013 as reported by Knittel et al but the frequency of detection of these two drugs tapered off in 2015 with AB‐CHMINACA taking the top spot and attributing for 19% of positive findings as reported by Tynon et al…”

Section: Resultssupporting

confidence: 89%

“…The low blood concentration of 5F‐ADB and AMB‐FUBINACA are consistent with reports where median concentration of related parent SCs in blood was at or below 1 ng/mL . 5F‐ADB was also detected in 70 post‐mortem blood samples at concentrations between 0.10 and 1.55 ng/mL, with a mean of 0.40 ng/mL …”

Section: Resultssupporting

confidence: 85%

“…This is consistent with the concentration range of 0.23–67.09 ng/mL as reported by Yeter et al, where 26 out of the 30 reported blood cases contained 5F‐ADB acid greater than 1 ng/mL . The same group also reported, in another publication, that 0.15–23.4 ng/mL (mean: 2.69 ng/mL) of 5F‐ADB acid was detected in 70 post‐mortem blood samples. The predominant presence and higher level of the acid metabolites relative to the parent indazole carboxamide compounds in blood is consistent with the reported rapid and extensive metabolic hydrolysis of the terminal ester moiety via esterase activity …”

Section: Resultssupporting

confidence: 85%

See 2 more Smart Citations

Simultaneous analysis of 29 synthetic cannabinoids and metabolites, amphetamines, and cannabinoids in human whole blood by liquid chromatography–tandem mass spectrometry – A New Zealand perspective of use in 2018

Ong

Kappatos

Russell

et al. 2019

Drug Testing and Analysis

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We describe the validation of a method for the simultaneous analysis of 29 synthetic cannabinoids (SCs) and metabolites, 4 amphetamines, and 2 cannabinoids in human whole blood. This method enables one analysis to cover what previously required multiple analyses for these classic and novel drugs-of-abuse with diverse physicochemical properties. The scope of targeted analytes was based on the most prevalent drugs-ofabuse and SCs encountered at the New Zealand border in 2017 and included parent compounds and metabolites belonging to the indole and indazole carboxamide, quinolinyl indole carboxylate, and naphthoylindole classifications. Samples were prepared by supported-liquid-extraction (SLE) followed by liquid chromatography −tandem mass spectrometry (LC−MS/MS) analysis with positive electrospray ionization (ESI). The method was validated with respect to selectivity, matrix effects, process efficiency, sensitivity, repeatability, extract stability, and carryover for qualitative confirmation. Linearity as well as accuracy and precision data at target decision concentrations were also evaluated. The limits of detection and confirmation ranged from 0.1 to 6.0 ng/mL and 1.0 to 6.0 ng/mL, respectively. The described method was successfully applied to the analysis of 564 ante-and post-mortem blood samples in 2018. There were 132 cases (23%) with positive findings of at least one SC, with the five most commonly detected SCs being AMB-FUBINACA and/or acid (61%), 5F-ADB and/or acid (40%), ADB-FUBINACA (11%), 5F-MDMB-PICA acid (6%), and MDMB-FUBINACA acid (6%). The results also demonstrate the predominant presence of metabolites at higher levels than the unchanged parent SCs in blood, highlighting the need to maintain forensic screening methods capable of the simultaneous detection of both parent compounds and metabolites.

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Section: Resultssupporting

confidence: 89%

Section: Resultssupporting

confidence: 85%

Section: Resultssupporting

confidence: 85%

See 1 more Smart Citation

Simultaneous analysis of 29 synthetic cannabinoids and metabolites, amphetamines, and cannabinoids in human whole blood by liquid chromatography–tandem mass spectrometry – A New Zealand perspective of use in 2018

Ong

Kappatos

Russell

et al. 2019

Drug Testing and Analysis

View full text Add to dashboard Cite

show abstract

“…A number of toxicology reports from Bulgaria, Germany, Japan, New Zealand, Spain, Turkey, and the United States have included overdose, drowning, driving under the influence of drugs (DUID), and prison inmate fatalities linked to the consumption of 5F-ADB. 27,34,[39][40][41][42][43][44][45][46][47][48][49][50][51][52] Analysis of human biological specimens for the presence of synthetic cannabinoids typically entails identifying the parent drug in blood specimens, and/or its metabolites in urine. 7 However, this approach is incomplete, as many synthetic cannabinoid metabolites have been determined to be pharmacologically active and also appear in blood samples.…”

Section: Introductionmentioning

confidence: 99%

“…7 However, this approach is incomplete, as many synthetic cannabinoid metabolites have been determined to be pharmacologically active and also appear in blood samples. 40,45,[53][54][55] It is important, therefore, to have a more complete understanding of how synthetic cannabinoid metabolites are distributed in vivo, especially in blood, and whether the predominant metabolites are pharmacologically active.…”

Section: Introductionmentioning

confidence: 99%

Metabolic profiling of synthetic cannabinoid 5F‐ADB and identification of metabolites in authentic human blood samples via human liver microsome incubation and ultra‐high‐performance liquid chromatography/high‐resolution mass spectrometry

Presley

Castaneto

Logan

et al. 2020

Rapid Comm Mass Spectrometry

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Indazole carboxamide synthetic cannabinoids, a prevalent class of recreational drugs, are a major clinical, forensic and public health challenge. One such compound, 5F-ADB, has been implicated in fatalities worldwide. Understanding its metabolism and distribution facilitates the development of laboratory assays to substantiate its consumption. Synthetic cannabinoid metabolites have been extensively studied in urine; studies identifying metabolites in blood are limited and no data on the metabolic stability (half-life, clearance and extraction ratio) of 5F-ADB have been published prior to this report. Methods: The in vitro metabolism of 5F-ADB was elucidated via incubation with human liver microsomes for 2 h at 37 C. Samples were collected at multiple time points to determine its metabolic stability. Upon identification of metabolites, authentic forensic human blood samples underwent liquid-liquid extraction and were screened for metabolites. Extracts were analyzed via ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/QTOFMS) operated in positive electrospray ionization mode. Results: Seven metabolites were identified including oxidative defluorination (M1); carboxypentyl (M2); monohydroxylation of the fluoropentyl chain (M3.1/M3.2) and indazole ring system (M4); ester hydrolysis (M5); and ester hydrolysis with oxidative defluorination (M6). The half-life (3.1 min), intrinsic clearance (256.2 mL min −1 kg −1), hepatic clearance (18.6 mL min −1 kg −1) and extraction ratio (0.93) were determined for the first time. In blood, M1 was present in each sample as the most abundant substance; two samples contained M5; one contained 5F-ADB, M1 and M5. Conclusions: 5F-ADB is rapidly metabolized in HLM. 5F-ADB, M1 and M5 are pharmacologically active at the cannabinoid receptors (CB 1 /CB 2) and M1 and M5 may contribute to a user's impairment profile. The results demonstrate that it is imperative that synthetic cannabinoid assays screen for pharmacologically active metabolites, especially for drugs with short half-lives. The authors propose that M1 and M5 are appropriate markers to include in laboratory blood tests screening for 5F-ADB.

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Diagnosing intake and rationalizing toxicities associated with 5F-MDMB-PINACA and 4F-MDMB-BINACA abuse

et al. 2020

View full text Add to dashboard Cite

Detection and quantification of 5F-ADB and its methyl ester hydrolysis metabolite in fatal intoxication cases by liquid chromatography–high resolution mass spectrometry

Cited by 19 publications

References 21 publications

Simultaneous analysis of 29 synthetic cannabinoids and metabolites, amphetamines, and cannabinoids in human whole blood by liquid chromatography–tandem mass spectrometry – A New Zealand perspective of use in 2018

Simultaneous analysis of 29 synthetic cannabinoids and metabolites, amphetamines, and cannabinoids in human whole blood by liquid chromatography–tandem mass spectrometry – A New Zealand perspective of use in 2018

Metabolic profiling of synthetic cannabinoid 5F‐ADB and identification of metabolites in authentic human blood samples via human liver microsome incubation and ultra‐high‐performance liquid chromatography/high‐resolution mass spectrometry

Diagnosing intake and rationalizing toxicities associated with 5F-MDMB-PINACA and 4F-MDMB-BINACA abuse

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