Identification of MT-45 Metabolites: In Silico Prediction, In Vitro Incubation with Rat Hepatocytes and In Vivo Confirmation
| Autor: | Federico Fanti, Adolfo Gregori, Isabella Canazza, Flaminia Vincenti, Gabriele Vannutelli, Matteo Marti, Anna Rita Togna, Camilla Montesano, Manuel Sergi |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
synthetic opioid substance abuse piperazines rat rat hepatocytes computer simulation Health Toxicology and Mutagenesis In silico Metabolite Socio-culturale Toxicology 01 natural sciences Piperazines Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Environmental Chemistry Animals Toxicology and Mutagenesis Computer Simulation Incubation Chemical Health and Safety Chemistry 010401 analytical chemistry Biological activity In vitro Hepatocytes Rats Substance Abuse Detection 0104 chemical sciences Metabolic pathway Biochemistry Health Glucuronide 030217 neurology & neurosurgery |
| Popis: | MT-45 is a synthetic opioid with a pharmacological activity comparable to morphine and it has been involved in intoxications and fatalities reported in Europe and in USA. It was recently subject to control measures, but to date the metabolic pathways of the substance are still unknown. Using rat hepatocytes and LC-HRMS, 14 novel Phase I and II MT-45 metabolites were identified, products of monohydroxylation, dihydroxylation and N-dealkylation; glucuronide conjugation of mono- and dihydroxylated metabolites also occurred. The detected metabolites were firstly predicted in silico, then incubation of the drug with rat hepatocytes was carried out and the obtained metabolites were identified by LC-HRMS, with retention times, mass shift between theoretical mass and observed mass ( |
| Databáze: | OpenAIRE |
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