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Quantification of low molecular weight selenium metabolites in human plasma after treatment with selenite in pharmacological doses by LC-ICP-MS

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Abstract

The paper presents an analytical method for quantification of low molecular weight (LMW) selenium compounds in human plasma based on liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS) and post column isotope dilution-based quantification. Prior to analysis, samples were ultrafiltrated using a cut-off value of 3000 Da. The method was validated in aqueous solution as well as plasma using standards of selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys), selenite, and the selenosugar Se-methylseleno-N-acetylgalactosamine (SeGal) for linearity, precision, recoveries, and limits of detection and quantitation with satisfactory results. The method was applied for analysis of a set of plasma samples from cancer patients receiving selenite treatment in a clinical trial. Three LMW selenium compounds were observed. The main compounds, SeGal and selenite were tentatively identified by retention time matching with standards in different chromatographic systems, while the third minor compound was not identified. The identity of the selenosugar was verified by ESI-MS-MS product ion scanning, while selenite was identified indirectly as the glutathione (GSH) reaction product, GS-Se-SG.

A method for analysing plasma samples based on spin filtering and LC-ICP-MS analysis with isotope dilution quantification was developed and applied to samples from patients receiving selenite in pharmacological doses in a clinical trial

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Acknowledgments

The authors wish to thank Erik Huusfeldt Larsen for the donation of the enriched 77Se solution and laboratory technician Camilla Jensen for skillful technical assistance.

The SECAR trial was supported by grants from Cancerfonden and Jochnick Foundation, Sweden.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Konstantina Flouda, Julie Maria Dersch, Charlotte Gabel-Jensen, Stefan Stürup & Bente Gammelgaard

  2. Division of Pathology F46, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden

    Sougat Misra & Mikael Björnstedt

Authors
  1. Konstantina Flouda
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  2. Julie Maria Dersch
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  3. Charlotte Gabel-Jensen
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  4. Stefan Stürup
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  5. Sougat Misra
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  6. Mikael Björnstedt
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  7. Bente Gammelgaard
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Corresponding author

Correspondence to Bente Gammelgaard.

Ethics declarations

The SECAR-trial [14] was approved by the Swedish Medical Products Agency and registered in the EU Clinical Trial Register (Eudra CT Number: 2006-004076-13) and by the Ethical Committee of Stockholm (2006/429-31/3).

Informed consent was given by the healthy volunteer donating the plasma sample for validation.

Conflict of interest

The authors declare that they have no conflict of interest.

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Flouda, K., Dersch, J.M., Gabel-Jensen, C. et al. Quantification of low molecular weight selenium metabolites in human plasma after treatment with selenite in pharmacological doses by LC-ICP-MS. Anal Bioanal Chem 408, 2293–2301 (2016). https://doi.org/10.1007/s00216-016-9325-2

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  • DOI: https://doi.org/10.1007/s00216-016-9325-2

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