Quantitative multiple fragment monitoring with enhanced in-source fragmentation/annotation mass spectrometry

Journal article (2023)

Authors

Samuel Bernardo-Bermejo Universidad de Alcalá
Jingchuan Xue Guangdong University of Technology
Linh Hoang Scripps Research Institute
Elizabeth Billings Scripps Research Institute
Bill Webb Scripps Research Institute
M. Willy Honders Leiden University Medical Center
Sanne Venneker Leiden University Medical Center
Bram Heijs Leiden University Medical Center
E.B. van den Akker Pattern Recognition and Bioinformatics - EEMCS , Leiden University Medical Center
Erik B. van den Akker Pattern Recognition and Bioinformatics - EEMCS , Leiden University Medical Center
E. B. van den Akker Pattern Recognition and Bioinformatics - EEMCS , Leiden University Medical Center
Erik Ben van den Akker Pattern Recognition and Bioinformatics - EEMCS , Leiden University Medical Center
Erik van den Akker Pattern Recognition and Bioinformatics - EEMCS , Leiden University Medical Center
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Research Group
Pattern Recognition and Bioinformatics (EEMCS) (TU Delft)
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Published Date

2023

Language

English

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Faculty

Electrical Engineering, Mathematics and Computer Science

Department

Intelligent Systems

Research Group

Pattern Recognition and Bioinformatics

Abstract

Analytical techniques with high sensitivity and selectivity are essential to the quantitative analysis of clinical samples. Liquid chromatography coupled to tandem mass spectrometry is the gold standard in clinical chemistry. However, tandem mass spectrometers come at high capital expenditure and maintenance costs. We recently showed that it is possible to generate very similar results using a much simpler single mass spectrometry detector by performing enhanced in-source fragmentation/annotation (EISA) combined with correlated ion monitoring. Here we provide a step-by-step protocol for optimizing the analytical conditions for EISA, so anyone properly trained in liquid chromatography–mass spectrometry can follow and apply this technique for any given analyte. We exemplify the approach by using 2-hydroxyglutarate (2-HG) which is a clinically relevant metabolite whose d-enantiomer is considered an ‘oncometabolite’, characteristic of cancers associated with mutated isocitrate dehydrogenases 1 or 2 (IDH1/2). We include procedures for determining quantitative robustness, and show results of these relating to the analysis of dl-2-hydroxyglutarate in cells, as well as in serum samples from patients with acute myeloid leukemia that contain the IDH1/2 mutation. This EISA–mass spectrometry protocol is a broadly applicable and low-cost approach for the quantification of small molecules that has been developed to work well for both single-quadrupole and time-of-flight mass analyzers.