Clinical determination of folates: recent analytical strategies and challenges

  • Jana Verstraete
  • Filip Kiekens
  • Simon Strobbe
  • Hans De Steur
  • Xavier Gellynck
  • Dominique Van Der Straeten
  • Christophe P. StoveEmail author
Part of the following topical collections:
  1. Young Investigators in (Bio-)Analytical Chemistry


Since the introduction of liquid chromatography tandem mass spectrometry in clinical laboratories, folate analysis has shifted from microbiological or protein-binding assays to chromatographic methods. Now, it is possible to sensitively and selectively determine several folate species in clinical samples where only a total folate content could be quantified using a microbiological or a binding assay. Although several chromatographic methods have been developed, validated, and published, interlaboratory variability limits the comparability of the results. In this review, we provide an overview of the latest strategies for sampling, sample treatment, and analysis and how these may influence the final analytical result. Among the variables covered are the effect of pH, temperature, and storage and the use of antioxidants and anticoagulants on analyte stability. In addition, we highlight the importance of correct assay calibration and the use of (labeled) certified reference materials in order to obtain correct and comparable results among different laboratories.

Graphical abstract


Folate Plasma Serum Red blood cell Chromatography Mass spectrometry 


Funding information

The folate research of the authors was supported by GOA 01G00409 and BOF18/GOA/042 (Bijzonder Onderzoeksfonds UGent), IWT.141529 (Agentschap voor Innovatie door Wetenschap en Technologie), and 1S61617N (Fonds voor Wetenschappelijk Onderzoek - Vlaanderen).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Jana Verstraete
    • 1
  • Filip Kiekens
    • 1
  • Simon Strobbe
    • 2
  • Hans De Steur
    • 3
  • Xavier Gellynck
    • 3
  • Dominique Van Der Straeten
    • 2
  • Christophe P. Stove
    • 1
    Email author
  1. 1.Laboratory of Toxicology, Department of Bio-AnalysisGhent UniversityGhentBelgium
  2. 2.Laboratory of Functional Plant Biology, Department of PhysiologyGhent UniversityGhentBelgium
  3. 3.Division Agri-Food Marketing & Chain Management, Department of Agricultural EconomicsGhent UniversityGhentBelgium

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