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Quantitative MALDI-MS/MS assay for serum cortisol through charged derivatization.

Masahiro Nakamura1, Marina Moritsuna1, Keita Yuda1

  • 1Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba, 278-8510, Japan.

Journal of Pharmaceutical and Biomedical Analysis
|October 15, 2019
PubMed
Summary

A new method accurately measures serum cortisol (CRT) using MALDI-MS/MS, a rapid technique. This advancement offers precise quantification for clinical diagnostics and research applications.

Keywords:
CortisolDerivatizationGirard-type reagentMatrix assisted laser desorption/ionization-tandem mass spectrometryQuantification

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Area of Science:

  • Endocrinology
  • Analytical Chemistry
  • Biochemistry

Background:

  • Cortisol (CRT) is a vital glucocorticoid hormone with significant clinical implications.
  • Accurate serum cortisol measurement is crucial for diagnosing various physiological and pathological conditions.
  • Existing methods for cortisol quantification may have limitations in terms of speed, sensitivity, or complexity.

Purpose of the Study:

  • To develop and validate a novel method for quantifying serum cortisol (CRT) using matrix-assisted laser desorption/ionization-tandem mass spectrometry (MALDI-MS/MS).
  • To enhance the sensitivity of MALDI-MS/MS for cortisol analysis through derivatization.
  • To assess the clinical applicability of the developed method by analyzing patient samples.

Main Methods:

  • Development of a serum cortisol quantification method utilizing MALDI-MS/MS.
  • Employing a Girard-type reagent (1-(hydrazinocarbonylmethyl)isoquinolinium chloride) for derivatization to improve sensitivity.
  • Validation of the method's reproducibility, measurable range, and agreement with established techniques (LC/ESI-MS/MS, ECLIA).

Main Results:

  • The developed MALDI-MS/MS method demonstrated reproducible quantification of serum cortisol with low intra- and inter-assay variability (≤7.4%).
  • The method established a measurable quantification range of 25-500 ng/mL for serum cortisol.
  • Serum cortisol levels determined by the new method showed excellent agreement with those obtained from liquid chromatography/electrospray ionization-MS/MS and electrochemiluminescence immunoassay.

Conclusions:

  • The developed derivatization-enhanced MALDI-MS/MS method provides a sensitive, specific, and rapid approach for serum cortisol quantification.
  • This method is suitable for analyzing clinical samples, including peripheral venous blood from healthy individuals and adrenal venous blood from patients with primary aldosteronism.
  • MALDI-MS/MS offers a promising alternative for routine clinical measurement of serum cortisol.