Tryptamines are not routinely detected in emergency department screening panels and are not routinely analyzed in forensic and clinical settings, resulting in incorrect interpretation of symptoms or autopsy findings. As a result, NPS metabolism profiling in vitro is critical for identifying specific consumption markers and elucidating the pharmacokinetic profile. This dissertation had two main objectives: Firstly, to assess the human metabolism of 4-AcO-DiPT, 4-OH-MPT, and α-MT and identify optimal intake biomarkers in clinical and forensic toxicology. Secondly, using international forensic toxicology guidelines, to develop and validate a comprehensive LC-HRMS/MS method to detect or, when possible, quantify tryptamines and metabolites in urine for forensic and clinical applications. The human metabolic fate of three tryptamines was studied using in silico metabolite predictions, LC-HRMS/MS, and software-assisted data mining in 10-donor-pooled human hepatocyte incubations and postmortem urine and blood, when available. The obtained results will help toxicologists identify new cases to generate biological samples to refine the current results and will provide important data to orient analytical standard manufacturers' synthesis effort. To identify positive cases in forensic and clinical toxicology, proper analytical methods for detecting tryptamines and metabolite biomarkers of consumption in biological matrices are required.
Le triptamine non vengono rilevate di routine nei pannelli di screening del pronto soccorso e non vengono analizzate di routine in contesti forensi e clinici, con conseguente interpretazione errata dei sintomi o risultati dell'autopsia. Di conseguenza, la profilazione del metabolismo NPS in vitro è fondamentale per identificare specifici marcatori di consumo e chiarire il profilo farmacocinetico. Questa dissertazione aveva due obiettivi principali: in primo luogo, valutare il metabolismo umano di 4-AcO-DiPT, 4-OH-MPT e α-MT e identificare biomarcatori di assunzione ottimali nella tossicologia clinica e forense. In secondo luogo, utilizzando le linee guida internazionali sulla tossicologia forense, per sviluppare e convalidare un metodo LC-HRMS/MS completo per rilevare o, quando possibile, quantificare triptamine e metaboliti nelle urine per applicazioni forensi e cliniche. Il destino metabolico umano di tre triptamine è stato studiato utilizzando previsioni di metaboliti in silico, LC-HRMS/MS e data mining assistito da software in incubazioni di epatociti umani in pool di 10 donatori e urina e sangue post mortem, quando disponibili. I risultati ottenuti aiuteranno i tossicologi a identificare nuovi casi per generare campioni biologici per perfezionare i risultati attuali e forniranno dati importanti per orientare lo sforzo di sintesi dei produttori di standard analitici. Per identificare i casi positivi in tossicologia forense e clinica, sono necessari metodi analitici adeguati per la rilevazione di triptamine e biomarcatori di metaboliti di consumo in matrici biologiche
Metabolism and analysis of new psychoactive substances / ROMÃO MALACA, SARA PATRÍCIA. - (2023 Jun 05).
Metabolism and analysis of new psychoactive substances
ROMÃO MALACA, SARA PATRÍCIA
2023-06-05
Abstract
Tryptamines are not routinely detected in emergency department screening panels and are not routinely analyzed in forensic and clinical settings, resulting in incorrect interpretation of symptoms or autopsy findings. As a result, NPS metabolism profiling in vitro is critical for identifying specific consumption markers and elucidating the pharmacokinetic profile. This dissertation had two main objectives: Firstly, to assess the human metabolism of 4-AcO-DiPT, 4-OH-MPT, and α-MT and identify optimal intake biomarkers in clinical and forensic toxicology. Secondly, using international forensic toxicology guidelines, to develop and validate a comprehensive LC-HRMS/MS method to detect or, when possible, quantify tryptamines and metabolites in urine for forensic and clinical applications. The human metabolic fate of three tryptamines was studied using in silico metabolite predictions, LC-HRMS/MS, and software-assisted data mining in 10-donor-pooled human hepatocyte incubations and postmortem urine and blood, when available. The obtained results will help toxicologists identify new cases to generate biological samples to refine the current results and will provide important data to orient analytical standard manufacturers' synthesis effort. To identify positive cases in forensic and clinical toxicology, proper analytical methods for detecting tryptamines and metabolite biomarkers of consumption in biological matrices are required.File | Dimensione | Formato | |
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