Arimistane: Degradation product or metabolite of 7-oxo-DHEA?

Arimistane : Degradation product or metabolite of 7-oxo-DHEA? / Dayamín Martínez Brito, Patrizia Leogrande, Cristiana Colamonici, Davide Curcio, Francesco Botre, Xavier de la Torre. - (Drug Testing and Analysis (2021) 30 March);

  • PMID: 33783974
  • DOI: 10.1002/dta.3036

Abstract

Rationale: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: 7-oxo-DHEA; arimistane; degradation product; liquid chromatography-mass spectrometry; metabolism.

Parameters

Science
Study
Date
30 March 2021
People
Botrè, Francesco
Colamonici, Cristiana
Curcio, Davide
de la Torre, Xavier
Leogrande, Patrizia
Martinez-Brito, Dayamin
Country
Italy
Switzerland
Language
English
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Université de Lausanne (UNIL) - University of Lausanne
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Roma, Italia: Laboratorio Antidoping FMSI
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Mass spectrometry analysis
Testing method development
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S4. Hormone And Metabolic Modulators
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7-keto-DHEA
Androsta-3,5-diene-7,17-dione (arimistane)
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Scientific article
Date generated
14 April 2021
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23 April 2021
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