Synthesis of steroid bisglucuronide and sulfate glucuronide reference materials: Unearthing neglected treasures of steroid metabolism

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• dc.contributor.author Pranata, Andy
• dc.contributor.author Fitzgerald, Christopher C.
• dc.contributor.author Khymenets, Olha, 1974-
• dc.contributor.author Westley, Erin
• dc.contributor.author Anderson, Natasha J.
• dc.contributor.author Ma, Paul
• dc.contributor.author Pozo Mendoza, Óscar J., 1975-
• dc.contributor.author McLeod, Malcolm D.
• dc.date.accessioned 2019-07-18T06:33:38Z
• dc.date.issued 2019
• dc.description.abstract Doubly or bisconjugated steroid metabolites have long been known as minor components of the steroid profile that have traditionally been studied by laborious and indirect fractionation, hydrolysis and gas chromatography-mass spectrometry (GC-MS) analysis. Recently, the synthesis and characterisation of steroid bis(sulfate) (aka disulfate or bis-sulfate) reference materials enabled the liquid chromatography-tandem mass spectrometry (LC-MS/MS) study of this metabolite class and the development of a constant ion loss (CIL) scan method for the direct and untargeted detection of steroid bis(sulfate) metabolites. Methods for the direct LC-MS/MS detection of other bisconjugated steroids, such as steroid bisglucuronide and mixed steroid sulfate glucuronide metabolites, have great potential to reveal a more complete picture of the steroid profile. However, access to steroid bisglucuronide or sulfate glucuronide reference materials necessary for LC-MS/MS method development, metabolite identification or quantification is severely limited. In this work, ten steroid bisglucuronide and ten steroid sulfate glucuronide reference materials were synthesised through an ordered combination of chemical sulfation and/or enzymatic glucuronylation reactions. All compounds were purified and characterised using NMR and MS methods. Chemistry for the preparation of stable isotope labelled steroid {13C6}-glucuronide internal standards has also been developed and applied to the preparation of two selectively mono-labelled steroid bisglucuronide reference materials used to characterise more completely MS fragmentation pathways. The electrospray ionisation and fragmentation of the bisconjugated steroid reference materials has been studied. Preliminary targeted ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis of the reference materials prepared revealed the presence of three steroid sulfate glucuronides as endogenous human urinary metabolites.
• dc.format.mimetype application/pdf
• dc.identifier.citation Pranata A, Fitzgerald CC, Khymenets O, Westley E, Anderson NJ, Ma P. et al. Synthesis of steroid bisglucuronide and sulfate glucuronide reference materials: Unearthing neglected treasures of steroid metabolism. Steroids. 2019 Mar;143:25-40. DOI: 10.1016/j.steroids.2018.11.017
• dc.identifier.doi http://dx.doi.org/10.1016/j.steroids.2018.11.017
• dc.identifier.issn 0039-128X
• dc.identifier.uri http://hdl.handle.net/10230/42033
• dc.language.iso eng
• dc.publisher Elsevier
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.steroids.2018.11.017
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Mass spectrometry
• dc.subject.keyword Phase II metabolism
• dc.subject.keyword Stable isotope labelled internal standard
• dc.subject.keyword Steroid bisglucuronide
• dc.subject.keyword Steroid conjugate
• dc.subject.keyword Steroid sulfate glucuronide
• dc.title Synthesis of steroid bisglucuronide and sulfate glucuronide reference materials: Unearthing neglected treasures of steroid metabolism
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion