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Metabolism study for CUMYL‐4CN‐BINACA in human hepatocytes and authentic urine specimens: Free cyanide is formed during the main metabolic pathway

Overview of attention for article published in Drug Testing and Analysis, April 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (70th percentile)
  • High Attention Score compared to outputs of the same age and source (80th percentile)

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6 X users
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1 Wikipedia page

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Title
Metabolism study for CUMYL‐4CN‐BINACA in human hepatocytes and authentic urine specimens: Free cyanide is formed during the main metabolic pathway
Published in
Drug Testing and Analysis, April 2018
DOI 10.1002/dta.2373
Pubmed ID
Authors

Anna Åstrand, Svante Vikingsson, Daniel Lindstedt, Gunilla Thelander, Henrik Gréen, Robert Kronstrand, Ariane Wohlfarth

Abstract

To further elucidate the metabolism of CUMYL-4CN-BINACA, a new synthetic cannabinoid with a cyano group, and to evaluate biomarkers, we incubated the substance in human hepatocytes and analysed nine authentic urine specimens. We also quantified CUMYL-4CN-BINACA and cyanide in blood and provide comprehensive data on the seven autopsy cases, five determined CUMYL-4CN-BINACA intoxications. For metabolite elucidation, CUMYL-4CN-BINACA was incubated with pooled human hepatocytes up to 5 h, urine samples were analysed with and without enzymatic hydrolysis. Data was acquired in data-dependent mode by UHPLC-HRMS with an Agilent 6550 QTOF. For quantitative analysis of CUMYL-4CN-BINACA, blood samples were precipitated and analysed by LC-MS/MS. Cyanide was determined by GC-headspace-NPD. CUMYL-4CN-BINACA was metabolized via CYP450-mediated hydroxylation at 4-butyl position generating a cyanohydrin (M12), which releases free cyanide to form an aldehyde intermediate and eventually generates 4-hydroxybutyl CUMYL-BINACA (M11) and CUMYL-BINACA butanoic acid (M10). Other minor metabolites were produced by hydroxylation, dihydroxylation, N-dealkylation and dihydrodiol formation; glucuronidation was observed. One urine sample showed high intensities of M10 and a wide variety of metabolites, the other samples contained fewer metabolites in low abundance and one sample showed no metabolites. CUMYL-4CN-BINACA blood concentrations ranged from 0.1-8.3 ng/g showing an overlap between fatal and non-fatal concentrations. One blood sample contained 0.36 μg/g cyanide. Release of free cyanide during metabolism is worrying as it might induce liver toxicity. As suggested earlier, CUMYL-BINACA butanoic acid is the most abundant biomarker in urine, but monitoring of additional metabolites or, even better, analysis for the parent in blood is recommended.

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X Demographics

The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 16 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 3 19%
Student > Bachelor 3 19%
Other 2 13%
Student > Master 1 6%
Unknown 7 44%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 3 19%
Environmental Science 2 13%
Immunology and Microbiology 1 6%
Sports and Recreations 1 6%
Chemistry 1 6%
Other 1 6%
Unknown 7 44%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 May 2018.
All research outputs
#5,987,485
of 24,453,338 outputs
Outputs from Drug Testing and Analysis
#334
of 1,433 outputs
Outputs of similar age
#88,890
of 300,972 outputs
Outputs of similar age from Drug Testing and Analysis
#7
of 35 outputs
Altmetric has tracked 24,453,338 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,433 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.0. This one has done well, scoring higher than 76% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 300,972 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 35 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.