Human metabolism and basic pharmacokinetic evaluation of AP‐238: a recently emerged acylpiperazine opioid
Abstract: As a consequence of recently implemented legal restrictions on fentanyl analogs, a new generation of acylpiperazine opioids appeared on the illicit drug market. AP-238 was the latest opioid in this series to be notified by the European Early Warning System in 2020 and was involved in an increasing number of acute intoxications. AP-238 metabolism was investigated to provide useful markers of consumption. For the tentative identification of the main phase I metabolites, a pooled human liver microsome assay was performed. Further, four whole blood and two urine samples collected during post-mortem examinations and samples from a controlled oral self-administration study were screened for anticipated metabolites. In total, 12 AP-238 phase I metabolites were identified through liquid chromatography-quadrupole time-of-flight mass spectrometry in the in vitro assay. All of these were confirmed in vivo, and additionally, 15 phase I and five phase II metabolites were detected in the human urine samples, adding up to a total of 32 metabolites. Most of these metabolites were also detected in the blood samples, although mostly with lower abundances. The main in vivo metabolites were built by hydroxylation combined with further metabolic reactions such as O-methylation or N-deacylation. The controlled oral self-administration allowed us to confirm the usefulness of these metabolites as proof of intake in abstinence control. The detection of metabolites is often crucial to documenting consumption, especially when small traces of the parent drug can be found in real samples. The in vitro assay proved to be suitable for the prediction of valid biomarkers of novel synthetic opioid intake
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Drug testing and analysis. - 16, 2 (2024) , 221-235, ISSN: 1942-7611
- Klassifikation
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Medizin, Gesundheit
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2023
- Urheber
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Brunetti, Pietro
Berardinelli, Diletta
Giorgetti, Arianna
Schwelm, Hannes Max
Haschimi, Belal
Pelotti, Susi
Busardò, Francesco Paolo
Auwärter, Volker
- DOI
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10.1002/dta.3535
- URN
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urn:nbn:de:bsz:25-freidok-2375888
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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25.03.2025, 13:53 MEZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Brunetti, Pietro
- Berardinelli, Diletta
- Giorgetti, Arianna
- Schwelm, Hannes Max
- Haschimi, Belal
- Pelotti, Susi
- Busardò, Francesco Paolo
- Auwärter, Volker
- Universität
Entstanden
- 2023