Please use this identifier to cite or link to this item: doi:10.22028/D291-33202
Title: Toxicokinetics and analytical toxicology of the abused opioid U-48800 - in vitro metabolism, metabolic stability, isozyme mapping, and plasma protein binding
Author(s): Gampfer, Tanja M.
Richter, Lilian H. J.
Schäper, Jan
Wagmann, Lea
Meyer, Markus R.
Language: English
Title: Drug Testing and Analysis
Volume: 11
Issue: 10
Pages: 1572–1580
Publisher/Platform: Wiley
Year of Publication: 2019
Free key words: LC−HRMS/MS
metabolic stability
new synthetic opioids
pooled human liver S9 fraction
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Due to the risk of new synthetic opioids (NSOs) for human health, the knowledge of their toxicokinetic characteristics is important for clinical and forensic toxicology. U‐48800 is an NSO structurally non‐related to classical opioids such as morphine or fentanyl and offered for abuse. As toxicokinetic data of U‐48800 is not currently available, the aims of this study were to identify the in vitro metabolites of U‐48800 in pooled human liver S9 fraction (pS9), to map the isozymes involved in the initial metabolic steps, and to determine further toxicokinetic data such as metabolic stability, including the in vitro half‐life (t1/2), and the intrinsic (CLint) and hepatic clearance (CLh). Furthermore, drug detectability studies in rat urine should be done using hyphenated mass spectrometry. In total, 13 phase I metabolites and one phase II metabolite were identified. N‐Dealkylation, hydroxylation, and their combinations were the predominant metabolic reactions. The isozymes CYP2C19 and CYP3A4 were mainly involved in these initial steps. CYP2C19 poor metabolizers may suffer from an increased U‐48800 toxicity. The in vitro t1/2 and CLint could be rated as moderate, compared to structural related compounds. After administration of an assumed consumer dose to rats, the unchanged parent compound was found only in very low abundance but three metabolites were detected additionally. Due to species differences, metabolites found in rats might be different from those in humans. However, phase I metabolites found in rat urine, the parent compound, and additionally the N‐demethyl metabolite should be used as main targets in toxicological urine screening approaches.
DOI of the first publication: 10.1002/dta.2683
Link to this record: urn:nbn:de:bsz:291--ds-332028
ISSN: 1942-7611
Date of registration: 4-Feb-2021
Description of the related object: Supporting Information
Related object:
Faculty: M - Medizinische Fakultät
Department: M - Experimentelle und Klinische Pharmakologie und Toxikologie
Professorship: M - Prof. Dr. Markus Meyer
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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