Date of Award

Spring 6-2026

Document Type

Thesis

Degree Name

Master of Science (MS)

Department/Program

Forensic Science

Language

English

First Advisor or Mentor

Marta Concheiro-Guisán

Second Reader

Ana Pego

Third Advisor

Eduardo Geraldo de Campos

Abstract

Psilocybin and its synthetic derivatives have emerged as compounds of interest in psychedelic-assisted therapy, but also as drugs of abuse. However, the instability of these compounds in biological matrices presents a substantial barrier to accurate clinical and forensic detection. This research focused on the evaluation of the stability of the tryptamine derivatives: psilacetin, 4-methylcarbonate-N,N-dipropyltryptamine (4-MeCO3-DPT),4-propionoxy-N,N-dimethyltryptamine (4-PrO-DMT) in blood and plasma under different storage conditions (time, preservatives, antioxidants). A key aim was to determine the concentration of ascorbic acid necessary to stabilize these compounds and prevent their oxidative degradation under various storage conditions and in the presence of different preservatives (NaF/KOx, EDTA, heparin, citrate), using LC-MS/MS analysis. Results demonstrated that in the absence of ascorbic acid, these synthetic prodrugs underwent nearly instantaneous and complete hydrolysis into psilocin or 4-OH-DPT within 15 to 30 minutes. In human whole blood, preservatives such as EDTA, heparin, and citrate failed to inhibit this degradation, resulting in rapid metabolic conversion. However, NaF/KOx was identified as the only preservative capable of inhibiting hydrolysis in human matrices when paired with 250 mM ascorbic acid. While 250 mM ascorbic acid was optimal for animal matrices such as sheep and bovine blood, 500 mM ascorbic acid was required to stabilize derivatives in rat blood and plasma.

Available for download on Thursday, May 25, 2028

Included in

Toxicology Commons

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