Evaluation of dermorphin metabolism using zebrafish water tank model and human liver microsomes

Evaluation of dermorphin metabolism using zebrafish water tank model and human liver microsomes / Juliana de L. Castro, Henrique M.G. Pereira, Valéria de Sousa, Maria Elvira P. Martucci. - (Current Drug Metabolism (2021) 15 February)

  • PMID: 33593255
  • DOI: 10.2174/1389200222666210216095753


Abstract

Background: Dermorphin is a heptapeptide with an analgesic potential higher than morphine that does not present the same risk for the development of tolerance. These pharmacological features make dermorphin a potential doping agent in competitive sports and is already prohibited for racehorses. For athletes, the development of an efficient strategy to monitor for its abuse necessitates an investigation of the metabolism of dermorphin in humans.

Methods: Here, human liver microsomes and zebrafish were utilized as model systems of human metabolism to evaluate the presence and kinetics of metabolites derived from dermorphin. Five hours after its administration, the presence of dermorphin metabolites could be detected in both models by liquid chromatography coupled to high resolution mass spectrometry.

Results: Although the two models showed common results, marked differences were also observed in relation to the formed metabolites. Six putative metabolites, based on their exact masses of m/z 479.1915, m/z 501.1733, m/z 495.1657, m/z 223.1073, m/z 180.1017 and m/z 457.2085, are proposed to represent the metabolic pattern of dermorphin. The major metabolite generated from the administration of dermorphin in both models was YAFG-OH (m/z 457.2085), which is the N-terminal tetrapeptide previously identified from studies with rats.

Conclusion: Its extensive characterization and commercial availability suggests that it could serve as a primary target analyte for the detection of dermorphin misuse. The metabolomics approach also allowed the assignment of other confirmatory metabolites.

Parameters

Science
Study
Date
15 February 2021
People
Castro, Juliana de L.
Martucci, Maria Elvira P.
Pereira, Henrique Marcelo Gualberto
Sousa, Valéria
Country
Brazil
Language
English
Other organisations
Universidade Federal de Ouro Preto (UFOP) - Federal University of Ouro Preto
Universidade Federal do Rio de Janeiro (UFRJ)- Federal University of Rio de Janeiro
Analytical aspects
Mass spectrometry analysis
Metabolization
New substance, not on prohibited list
Doping classes
S7. Narcotics
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Date generated
18 March 2021
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20 March 2021
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