Screening of in vitro synthesised metabolites of 4,9,11-trien-3-one steroids by liquid chromatography mass spectrometry.

Détails

ID Serval
serval:BIB_426E0BDB3E40
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Screening of in vitro synthesised metabolites of 4,9,11-trien-3-one steroids by liquid chromatography mass spectrometry.
Périodique
European journal of mass spectrometry (Chichester, England)
Auteur⸱e⸱s
Kuuranne T., Pystynen K.H., Thevis M., Leinonen A., Schänzer W., Kostiainen R.
ISSN
1469-0667 (Print)
ISSN-L
1469-0667
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
14
Numéro
3
Pages
181-189
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The aim of the work was to develop a flexible in vitro synthesis procedure, which can be applied in order to study and predict the metabolic patterns of new derivatives of anabolic androgenic steroids (AAS) with respect to most prominent target compounds for doping control purposes. Microsomal and S9 fraction of human liver preparations were used as a source of metabolising enzymes and the co-substrates of the synthesis mixture were selected to favour phase-I metabolic reactions and glucuronidation as phase-II conjugation reactions. Model compounds within the study were 4,9,11-trien-3-one steroids, structural derivatives of gestrinone and trenbolone, which both are included in the list of prohibited compounds in sports by the World Anti-Doping Agency (WADA). The correlation between in vitro metabolism of human microsomes and in vivo excretion studies in human was compared with gestrinone and subsequently, the applicability of the in vitro model for prediction of AAS metabolic pathways for new doping agents was evaluated. All the AAS examined within this study were successfully metabolised using the developed in vitro model, hydroxylation, reduction and glucuronide conjugation being the most prominent reaction pathways. Hydroxylated and glucuronide-conjugated metabolites of in vivo experiment with gestrinone were the same metabolites formed in the enzyme-driven process, thus showing good in vitro-in vivo correlation. Liquid chromatographic-mass spectrometric and tandem mass spectrometric methods were developed, relying on the positive polarity of electrospray ionisation, which also allowed the direct detection of intact glucuronide-conjugated AAS metabolites. Due to charge delocalisation and high proton affinity, the developed method was proven effective in the analysis of AAS metabolites bearing extensive conjugated double bond systems in their structures.

Mots-clé
Adult, Anabolic Agents/pharmacokinetics, Anabolic Agents/urine, Chromatography, High Pressure Liquid, Doping in Sports, Gestrinone/analogs & derivatives, Gestrinone/pharmacokinetics, Gestrinone/urine, Glucuronides/chemistry, Glucuronides/urine, Humans, Hydroxylation, In Vitro Techniques, Male, Microsomes, Liver/enzymology, Oxidation-Reduction, Ribosomal Proteins/metabolism, Spectrometry, Mass, Electrospray Ionization/methods, Substance Abuse Detection/methods, Trenbolone Acetate/analogs & derivatives, Trenbolone Acetate/pharmacokinetics, Trenbolone Acetate/urine
Pubmed
Web of science
Création de la notice
02/05/2017 15:17
Dernière modification de la notice
20/08/2019 14:44
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