Dataset Information

Untargeted Metabolic Profiling of 4-Fluoro-Furanylfentanyl and Isobutyrylfentanyl in Mouse Hepatocytes and Urine by Means of LC-HRMS.

ABSTRACT: The diffusion of new psychoactive substances (NPS) is highly dynamic and the available substances change over time, resulting in forensic laboratories becoming highly engaged in NPS control. In order to manage NPS diffusion, efficient and innovative legal responses have been provided by several nations. Metabolic profiling is also part of the analytical fight against NPS, since it allows us to identify the biomarkers of drug intake which are needed for the development of suitable analytical methods in biological samples. We have recently reported the characterization of two new analogs of fentanyl, i.e., 4-fluoro-furanylfentanyl (4F-FUF) and isobutyrylfentanyl (iBF), which were found for the first time in Italy in 2019; 4F-FUF was identified for the first time in Europe and was notified to the European Early Warning System. The goal of this study was the characterization of the main metabolites of both drugs by in vitro and in vivo experiments. To this end, incubation with mouse hepatocytes and intraperitoneal administration to mice were carried out. Samples were analyzed by means of liquid chromatography-high resolution mass spectrometry (LC-HRMS), followed by untargeted data evaluation using Compound Discoverer software with a specific workflow, designed for the identification of the whole metabolic pattern, including unexpected metabolites. Twenty metabolites were putatively annotated for 4-FFUF, with the dihydrodiol derivative appearing as the most abundant, whereas 22 metabolites were found for iBF, which was mainly excreted as nor-isobutyrylfentanyl. N-dealkylation of 4-FFUF dihydrodiol and oxidation to carbonyl metabolites for iBF were also major biotransformations. Despite some differences, in general there was a good agreement between in vitro and in vivo samples.

SUBMITTER: Montesano C

PROVIDER: S-EPMC7916627 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Untargeted Metabolic Profiling of 4-Fluoro-Furanylfentanyl and Isobutyrylfentanyl in Mouse Hepatocytes and Urine by Means of LC-HRMS.

Montesano Camilla C Vincenti Flaminia F Fanti Federico F Marti Matteo M Bilel Sabrine S Togna Anna Rita AR Gregori Adolfo A Di Rosa Fabiana F Sergi Manuel M

Metabolites 20210210 2

The diffusion of new psychoactive substances (NPS) is highly dynamic and the available substances change over time, resulting in forensic laboratories becoming highly engaged in NPS control. In order to manage NPS diffusion, efficient and innovative legal responses have been provided by several nations. Metabolic profiling is also part of the analytical fight against NPS, since it allows us to identify the biomarkers of drug intake which are needed for the development of suitable analytical meth ...[more]

PMID: 33578841

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Project description:BackgroundThe nasal mucosa, as a primary site of entry for inhaled substances, contains both inhaled xenobiotic and endogenous biomarkers. Nasal mucosa can be non-invasively sampled (nasal epithelial lining fluid "NELF") and analyzed for biological mediators. However, methods for untargeted analysis of compounds inhaled and/or retained in the nasal mucosa are needed.ObjectivesThis study aimed to develop a high resolution LC-MS untargeted method to analyze collected NELF. Profiling of compounds in NELF samples will also provide baseline data for future comparative studies to reference.MethodsExtracted NELF analytes were injected to LC-ESI-MS. After spectrum processing, an in-house library provided annotations with high confidence, while more tentative annotation proposals were obtained via ChemSpider database matching.ResultsThe established method successfully detected unique molecular signatures within NELF. Baseline profiling of 27 samples detected 2002 unknown molecules, with 77 and 463 proposed structures by our in-house library and Chemspider matching. High confidence annotations revealed common metabolites and tentative annotations implied various environmental exposure biomarkers are also present in NELF.SignificanceThe experimental pipeline for analyzing NELF samples serves as simple and robust method applicable for future studies to characterize identities/effects of inhaled substances and metabolites retained in the nasal mucosa.Impact statementThe nasal mucosa contains exogenous and endogenous compounds. The development of an untargeted analysis is necessary to characterize the nasal exposome by deciphering the identity and influence of inhaled compounds on nasal mucosal biology. This study established a high resolution LC-MS based untargeted analysis of non-invasively collected nasal epithelial lining fluid. Baseline profiling of the nasal mucosa (n = 27) suggests the presence of environmental pollutants, along with detection of endogenous metabolites. Our results show high potential for the analytical pipeline to facilitate future respiratory health studies involving inhaled pollutants or pharmaceutical compounds and their effects on respiratory biology.

Dataset Information

Untargeted Metabolic Profiling of 4-Fluoro-Furanylfentanyl and Isobutyrylfentanyl in Mouse Hepatocytes and Urine by Means of LC-HRMS.

Publications

Untargeted Metabolic Profiling of 4-Fluoro-Furanylfentanyl and Isobutyrylfentanyl in Mouse Hepatocytes and Urine by Means of LC-HRMS.

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