dc.contributor.author
Kollmeier, Annette Sophie
dc.contributor.author
Torre, Xavier de la
dc.contributor.author
Müller, Christian
dc.contributor.author
Botrè, Francesco
dc.contributor.author
Parr, Maria Kristina
dc.date.accessioned
2020-10-19T09:25:15Z
dc.date.available
2020-10-19T09:25:15Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/28566
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-28315
dc.description.abstract
Rationale:
The aromatase inhibitor formestane (4‐hydroxyandrost‐4‐ene‐3,17‐dione) is included in the World Anti‐Doping Agency's List of Prohibited Substances in Sport. However, it also occurs endogenously as do its 2‐, 6‐ and 11‐hydroxy isomers. The aim of this study is to distinguish the different isomers using gas chromatography/electron ionization mass spectrometry (GC/EI‐MS) for enhanced confidence in detection and selectivity for determination.
Methods:
Established derivatization protocols to introduce [2H9]TMS were followed to generate perdeuterotrimethylsilylated and mixed deuterated derivatives for nine different hydroxy steroids, all with 3‐keto‐4‐ene structure. Formestane was additionally labelled with H218O to obtain derivatives doubly labelled with [2H9]TMS and 18O. GC/EI‐MS spectra of labelled and unlabelled TMS derivatives were compared. Proposals for the generation of fragment ions were substantiated by high‐resolution MS (GC/QTOFMS) and tandem mass spectrometry (MS/MS) experiments.
Results:
Subclass‐specific fragment ions include m/z 319 for the 6‐hydroxy and m/z 219 for the 11‐hydroxy compounds. Ions at m/z 415, 356, 341, 313, 269 and 267 were indicative for the 2‐ and 4‐hydroxy compounds. For their discrimination the transition m/z 503 → 269 was selective for formestane. In 2‐, 4‐ and 6‐hydroxy steroids loss of a TMSO radical takes place as cleavage of a TMS‐derived methyl radical and a neutral loss of (CH3)2SiO. Further common fragments were also elucidated.
Conclusions:
With the help of stable isotope labelling, the structures of postulated diagnostic fragment ions for the different steroidal subclasses were elucidated. 18O‐labelling of the other compounds will be addressed in future studies to substantiate the obtained findings. To increase method sensitivity MS3 may be suitable in future bioanalytical applications requiring discrimination of the 2‐ and 4‐hydroxy compounds.
en
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
hromatography/tandem mass spectrometry fragmentation
en
dc.subject
mass spectral discrimination
en
dc.subject
isomeric 3‐keto‐4‐ene hydroxy steroids
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::540 Chemie::540 Chemie und zugeordnete Wissenschaften
dc.title
In‐depth gas chromatography/tandem mass spectrometry fragmentation analysis of formestane and evaluation of mass spectral discrimination of isomeric 3‐keto‐4‐ene hydroxy steroids
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
e8937
dcterms.bibliographicCitation.doi
10.1002/rcm.8937
dcterms.bibliographicCitation.journaltitle
Rapid Communications in Mass Spectrometry
dcterms.bibliographicCitation.number
24
dcterms.bibliographicCitation.volume
34
dcterms.bibliographicCitation.url
https://doi.org/10.1002/rcm.8937
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Pharmazie
refubium.affiliation.other
Institut für Chemie und Biochemie
refubium.funding
DEAL Wiley
refubium.note.author
Die Publikation wurde aus Open Access Publikationsgeldern der Freien Universität Berlin gefördert.
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1097-0231