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Erschienen in: Forensic Toxicology 1/2020

31.07.2019 | Original Article

Pharmacokinetic study of xylazine in a zebrafish water tank, a human-like surrogate, by liquid chromatography Q-Orbitrap mass spectrometry

verfasst von: Rebecca Rodrigues Matos, Maria Elvira Poleti Martucci, Carina Souza de Anselmo, Francisco Radler Alquino Neto, Henrique Marcelo Gualberto Pereira, Vinícius Figueiredo Sardela

Erschienen in: Forensic Toxicology | Ausgabe 1/2020

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Abstract

Purpose

This study aims to investigate a zebrafish (Danio Rerio) water tank (ZWT) as an alternative model for the study of the metabolism of xylazine.

Methods

The ZWT approach for the study of metabolism consisted of two aquariums, where 18 fish and xylazine were added into the first tank. The second one, with 18 fish without drug, served as a negative control. The samples were submitted to a comprehensive analytical method developed for doping control purposes by liquid chromatography (LC) coupled with high-resolution mass spectrometry (HRMS) operating in five different acquisition modes. Glycoconjugate metabolites were evaluated indirectly by extracting the samples with and without the enzymatic hydrolysis step using β-glucuronidase.

Results

In total, 11 phase I and II metabolites were detected and characterized, of which four were previously described for humans and two for horses, and five metabolites were described for the first time. The main metabolites were 4-hydroxylated (M2) and oxygenated (M1) derivatives. Both metabolites were suggested as analytical targets for xylazine misuse. Around 79% of para- and meta-hydroxylated derivatives were in glycoconjugate form, whereas for oxo-hydroxylated and sulfone-hydroxylated derivatives of xylazine, around 83% and 70% were metabolized to the glycoconjugate form, respectively.

Conclusions

Xylazine was the subject of extensive metabolism in zebrafish. 4-Hydroxylated (M2) and oxygenated (M1) derivatives were the most abundant phase I metabolites as the main targets for doping control.
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Metadaten
Titel
Pharmacokinetic study of xylazine in a zebrafish water tank, a human-like surrogate, by liquid chromatography Q-Orbitrap mass spectrometry
verfasst von
Rebecca Rodrigues Matos
Maria Elvira Poleti Martucci
Carina Souza de Anselmo
Francisco Radler Alquino Neto
Henrique Marcelo Gualberto Pereira
Vinícius Figueiredo Sardela
Publikationsdatum
31.07.2019
Verlag
Springer Singapore
Erschienen in
Forensic Toxicology / Ausgabe 1/2020
Print ISSN: 1860-8965
Elektronische ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-019-00493-y

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