Arimistane: Degradation product or metabolite of 7-oxo-DHEA?
Détails
ID Serval
serval:BIB_E5853F9D6A8F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Arimistane: Degradation product or metabolite of 7-oxo-DHEA?
Périodique
Drug testing and analysis
ISSN
1942-7611 (Electronic)
ISSN-L
1942-7603
Statut éditorial
Publié
Date de publication
07/2021
Peer-reviewed
Oui
Volume
13
Numéro
7
Pages
1430-1439
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
The instability of androst-5-ene-3,7-dione structures under acidic conditions is known. The formation of arimistane from 7-oxo-DHEA, influenced by the conditions of sample extraction, and mainly derivatization reaction and gas chromatography (GC) injector temperature, was described earlier, potentially leading to misinterpretation of results. By using a liquid chromatography (LC)-mass spectrometry (MS) (LC-MS) we investigated the stability of the 7-oxo-DHEA in two different solvents (methanol and dimethyl sulfoxide [DMSO]), and the arimistane formation after the application common analytical procedures. Additionally, in vitro and in vivo studies of 7-oxo-DHEA were performed.
The stability of 7-oxo-DHEA was studied in solutions after 60 days storage at -20°C. In vitro studies were performed by incubating 7-oxo-DHEA with human liver microsomes (HLMs). Healthy volunteers collected urine samples before and after the administration of a single dose of 7-oxo-DHEA. Analyses were performed using high-performance LC (HPLC) coupled to a triple quadrupole mass spectrometer (MS/MS) and GC combustion isotope ratio mass spectrometry (GC-C-IRMS) following HPLC purification.
7-oxo-DHEA was stable after 60 days in DMSO while a protic solvent as methanol promotes the degradation of 7-oxo-DHEA to arimistane. HLM incubations showed no formation of arimistane and the sample preparation only influenced the degradation of 7-oxo-DHEA when solvolysis was applied. After the administration study the presence of arimistane also after the hydrolysis with β-glucuronidase (Escherichia coli) was observed while using β-glucuronidase/arylsulfatase (Helix pomatia) showed the presence of arimistane already in blank samples collected before administration.
Our results confirm arimistane as a valuable diagnostic marker of 7-oxo-DHEA administration, but also indicate that its formation is due to degradation processes rather than to metabolic biotransformation reactions.
The stability of 7-oxo-DHEA was studied in solutions after 60 days storage at -20°C. In vitro studies were performed by incubating 7-oxo-DHEA with human liver microsomes (HLMs). Healthy volunteers collected urine samples before and after the administration of a single dose of 7-oxo-DHEA. Analyses were performed using high-performance LC (HPLC) coupled to a triple quadrupole mass spectrometer (MS/MS) and GC combustion isotope ratio mass spectrometry (GC-C-IRMS) following HPLC purification.
7-oxo-DHEA was stable after 60 days in DMSO while a protic solvent as methanol promotes the degradation of 7-oxo-DHEA to arimistane. HLM incubations showed no formation of arimistane and the sample preparation only influenced the degradation of 7-oxo-DHEA when solvolysis was applied. After the administration study the presence of arimistane also after the hydrolysis with β-glucuronidase (Escherichia coli) was observed while using β-glucuronidase/arylsulfatase (Helix pomatia) showed the presence of arimistane already in blank samples collected before administration.
Our results confirm arimistane as a valuable diagnostic marker of 7-oxo-DHEA administration, but also indicate that its formation is due to degradation processes rather than to metabolic biotransformation reactions.
Mots-clé
Adult, Chromatography, Liquid/methods, Dehydroepiandrosterone/analogs & derivatives, Dehydroepiandrosterone/chemistry, Dehydroepiandrosterone/metabolism, Dimethyl Sulfoxide/chemistry, Doping in Sports/prevention & control, Drug Stability, Female, Humans, Male, Mass Spectrometry/methods, Methanol/chemistry, Microsomes, Liver/metabolism, Middle Aged, Solvents/chemistry, 7-oxo-DHEA, arimistane, degradation product, liquid chromatography-mass spectrometry, metabolism
Pubmed
Web of science
Création de la notice
04/01/2022 10:44
Dernière modification de la notice
05/05/2023 6:57