Untargeted Metabolic Profiling of 4-Fluoro-Furanylfentanyl and Isobutyrylfentanyl in Mouse Hepatocytes and Urine by Means of LC-HRMS
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 nati...
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MDPI AG
2021-02-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/11/2/97 |
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| author | Camilla Montesano Flaminia Vincenti Federico Fanti Matteo Marti Sabrine Bilel Anna Rita Togna Adolfo Gregori Fabiana Di Rosa Manuel Sergi |
| author_facet | Camilla Montesano Flaminia Vincenti Federico Fanti Matteo Marti Sabrine Bilel Anna Rita Togna Adolfo Gregori Fabiana Di Rosa Manuel Sergi |
| author_sort | Camilla Montesano |
| collection | DOAJ |
| description | 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 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 4F-FUF, with the dihydrodiol derivative appearing as the most abundant, whereas 22 metabolites were found for iBF, which was mainly excreted as nor-isobutyrylfentanyl. <i>N</i>-dealkylation of 4F-FUF 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. |
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| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T04:48:30Z |
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| series | Metabolites |
| spelling | doaj.art-0e57060e1b19467490af9cd08c6f87fd2023-12-03T13:12:03ZengMDPI AGMetabolites2218-19892021-02-011129710.3390/metabo11020097Untargeted Metabolic Profiling of 4-Fluoro-Furanylfentanyl and Isobutyrylfentanyl in Mouse Hepatocytes and Urine by Means of LC-HRMSCamilla Montesano0Flaminia Vincenti1Federico Fanti2Matteo Marti3Sabrine Bilel4Anna Rita Togna5Adolfo Gregori6Fabiana Di Rosa7Manuel Sergi8Department of Chemistry, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Chemistry, Sapienza University of Rome, 00185 Rome, ItalyFaculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, 64100 Teramo, ItalyDepartment of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, ItalyDepartment of Physiology and Pharmacology Vittorio Erspamer, Sapienza University of Rome, 00185 Rome, ItalyCarabinieri, Department of Scientific Investigation (RIS), 00191 Rome, ItalyCarabinieri, Department of Scientific Investigation (RIS), 00191 Rome, ItalyFaculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, 64100 Teramo, ItalyThe 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 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 4F-FUF, with the dihydrodiol derivative appearing as the most abundant, whereas 22 metabolites were found for iBF, which was mainly excreted as nor-isobutyrylfentanyl. <i>N</i>-dealkylation of 4F-FUF 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.https://www.mdpi.com/2218-1989/11/2/97fentanyl analogsmetabolic profileliquid chromatography-high resolution mass spectrometryin vitro and in vivo metabolismnew psychoactive substances |
| spellingShingle | Camilla Montesano Flaminia Vincenti Federico Fanti Matteo Marti Sabrine Bilel Anna Rita Togna Adolfo Gregori Fabiana Di Rosa Manuel Sergi Untargeted Metabolic Profiling of 4-Fluoro-Furanylfentanyl and Isobutyrylfentanyl in Mouse Hepatocytes and Urine by Means of LC-HRMS Metabolites fentanyl analogs metabolic profile liquid chromatography-high resolution mass spectrometry in vitro and in vivo metabolism new psychoactive substances |
| title | Untargeted Metabolic Profiling of 4-Fluoro-Furanylfentanyl and Isobutyrylfentanyl in Mouse Hepatocytes and Urine by Means of LC-HRMS |
| title_full | Untargeted Metabolic Profiling of 4-Fluoro-Furanylfentanyl and Isobutyrylfentanyl in Mouse Hepatocytes and Urine by Means of LC-HRMS |
| title_fullStr | Untargeted Metabolic Profiling of 4-Fluoro-Furanylfentanyl and Isobutyrylfentanyl in Mouse Hepatocytes and Urine by Means of LC-HRMS |
| title_full_unstemmed | Untargeted Metabolic Profiling of 4-Fluoro-Furanylfentanyl and Isobutyrylfentanyl in Mouse Hepatocytes and Urine by Means of LC-HRMS |
| title_short | Untargeted Metabolic Profiling of 4-Fluoro-Furanylfentanyl and Isobutyrylfentanyl in Mouse Hepatocytes and Urine by Means of LC-HRMS |
| title_sort | untargeted metabolic profiling of 4 fluoro furanylfentanyl and isobutyrylfentanyl in mouse hepatocytes and urine by means of lc hrms |
| topic | fentanyl analogs metabolic profile liquid chromatography-high resolution mass spectrometry in vitro and in vivo metabolism new psychoactive substances |
| url | https://www.mdpi.com/2218-1989/11/2/97 |
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