FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4291291520> ?p ?o ?g. }

• W4291291520 endingPage "S56" @default.
• W4291291520 startingPage "S56" @default.
• W4291291520 abstract "The main metabolites of methoxpropamine (MXPr) and the evaluation of their formation and excretion over time, using biological samples from mice, was investigated. MXPr is an arylcyclohexylamine dissociative drug structurally similar to 3-MeO-PCE, ketamine and deschloroketamine, which was recently identified on the European illegal market and added to the class of New Psychoactive Substances (NPS). Forensic laboratories are often required to identify new drugs and their metabolites, albeit the latter are yet not known or their reference standards are lacking. Therefore, we performed the investigation of methoxpropamine (MXPr) metabolism, in order to elucidate the distribution of the parent drug and its metabolites in urine and plasma over time. Furthermore, body hair was collected and analysed. Initially, urine samples from 16 mice were collected every hour for 6 consecutive hours. Furthermore, one sample was collected after 12 and 24 hours from the administration of increasing doses of MXPr (1-3-10 mg/kg). After 16 days of wash out, two doses of 1 and 3 mg/kg were administered and plasma samples were collected. After adding ketamine-d4, urine and plasma were diluted 1:3 with methanol/acetonitrile (95:5) and 5 μL were injected into the UHPLC-QTOF-HRMS. Based on the typical phase I and II metabolic reaction, the metabolic pattern was hypothesized. The tentative metabolites were identified by means of the fragmentation patterns, the exact masses of both their precursor and fragment ions. Finally, body hair collected one month before and after the injection of MXPr was analyzed following a specific procedure for keratin matrix. A wide array of metabolites was identified in urine, including normethoxpropamine, desmethylmethoxpropamine, dihydromethoxpropamine, desmethyl-normethoxpropamine, dihydro-desmethylmethoxpropamine and phase II glucuronide conjugates. Furthermore, the metabolic pathway that produces desmethylmethoxpropamine-glucoronide was identified as the preferential pathway for the elimination of MXPr from the body. In fact, 1 h after the administration, an abundant peak of excretion was observed with an average intensity 16 times higher than the free phase desmetyl-MXPr. The presence of normethoxpropamine (NorMXPr) in urine and plasma is also relevant, following the typical metabolic pathways based on dealkylation. Since norketamine is known to be pharmacologically active, so it may be for NorMXPr, thus probably contributing to the toxicity of this substance. In addition, desmethylmethoxpropamine-glucoronide, together with other minor products of metabolism, were detectable in urine up to 24 h after injection. Finally, MXPr and the major phase I metabolites were observed also in plasma (average concentration for the parent drug: 1.0 ng/mL) and hair (average concentration for the parent drug: 0.18 ng/mg). Few phases I and II metabolites were confirmed to be present in body hair, approximately one month after body administration. Some interesting differences were observed in the metabolites generated over time between female and male mice, a phenomenon that could be related to sexually dimorphic metabolism, both involving phase I and phase II enzymes. A comprehensive workflow for the detection of MXPr and its I and II phase metabolites are presented. Data acquisition included a TOF-MS high-resolution scan combined with TOF-MS/MS acquisition and demonstrated a considerable capability to detect and identify target compounds with high resolution levels. Thanks to this study, the identification of MXPr metabolites and their excretion times from the body was possible. The introduction of new target compounds will improve the efficiency of toxicological screening analysis on real samples and will extend the window of detection of the dissociative drug MXPr in biological matrices. In the future, human urine samples will be analyzed to confirm the detectability of the tentative metabolites." @default.
• W4291291520 created "2022-08-14" @default.
• W4291291520 creator A5025757801 @default.
• W4291291520 creator A5042476399 @default.
• W4291291520 creator A5047712543 @default.
• W4291291520 creator A5048884980 @default.
• W4291291520 creator A5073656514 @default.
• W4291291520 creator A5074688749 @default.
• W4291291520 creator A5082929329 @default.
• W4291291520 creator A5086748433 @default.
• W4291291520 date "2022-09-01" @default.
• W4291291520 modified "2023-10-05" @default.
• W4291291520 title "Metabolic study of methoxpropamine (MXPr) in mice and determination of its metabolites in biological samples by UHPLC-QTOF-HRMS" @default.
• W4291291520 doi "https://doi.org/10.1016/j.toxac.2022.06.069" @default.
• W4291291520 hasPublicationYear "2022" @default.
• W4291291520 type Work @default.
• W4291291520 citedByCount "0" @default.
• W4291291520 crossrefType "journal-article" @default.
• W4291291520 hasAuthorship W4291291520A5025757801 @default.
• W4291291520 hasAuthorship W4291291520A5042476399 @default.
• W4291291520 hasAuthorship W4291291520A5047712543 @default.
• W4291291520 hasAuthorship W4291291520A5048884980 @default.
• W4291291520 hasAuthorship W4291291520A5073656514 @default.
• W4291291520 hasAuthorship W4291291520A5074688749 @default.
• W4291291520 hasAuthorship W4291291520A5082929329 @default.
• W4291291520 hasAuthorship W4291291520A5086748433 @default.
• W4291291520 hasBestOaLocation W42912915201 @default.
• W4291291520 hasConcept C185592680 @default.
• W4291291520 hasConcept C2777477808 @default.
• W4291291520 hasConcept C2780026642 @default.
• W4291291520 hasConcept C2780035454 @default.
• W4291291520 hasConcept C2780795376 @default.
• W4291291520 hasConcept C42219234 @default.
• W4291291520 hasConcept C43617362 @default.
• W4291291520 hasConcept C55493867 @default.
• W4291291520 hasConcept C62231903 @default.
• W4291291520 hasConcept C71924100 @default.
• W4291291520 hasConcept C98274493 @default.
• W4291291520 hasConceptScore W4291291520C185592680 @default.
• W4291291520 hasConceptScore W4291291520C2777477808 @default.
• W4291291520 hasConceptScore W4291291520C2780026642 @default.
• W4291291520 hasConceptScore W4291291520C2780035454 @default.
• W4291291520 hasConceptScore W4291291520C2780795376 @default.
• W4291291520 hasConceptScore W4291291520C42219234 @default.
• W4291291520 hasConceptScore W4291291520C43617362 @default.
• W4291291520 hasConceptScore W4291291520C55493867 @default.
• W4291291520 hasConceptScore W4291291520C62231903 @default.
• W4291291520 hasConceptScore W4291291520C71924100 @default.
• W4291291520 hasConceptScore W4291291520C98274493 @default.
• W4291291520 hasIssue "3" @default.
• W4291291520 hasLocation W42912915201 @default.
• W4291291520 hasOpenAccess W4291291520 @default.
• W4291291520 hasPrimaryLocation W42912915201 @default.
• W4291291520 hasRelatedWork W1976626766 @default.
• W4291291520 hasRelatedWork W1984052295 @default.
• W4291291520 hasRelatedWork W1990694197 @default.
• W4291291520 hasRelatedWork W2008651038 @default.
• W4291291520 hasRelatedWork W2043524890 @default.
• W4291291520 hasRelatedWork W2067134005 @default.
• W4291291520 hasRelatedWork W2067605410 @default.
• W4291291520 hasRelatedWork W2072164925 @default.
• W4291291520 hasRelatedWork W2409773942 @default.
• W4291291520 hasRelatedWork W3021100874 @default.
• W4291291520 hasVolume "34" @default.
• W4291291520 isParatext "false" @default.
• W4291291520 isRetracted "false" @default.
• W4291291520 workType "article" @default.