On-Tissue Chemical Derivatization of Catecholamines Using 4-(N-Methyl)pyridinium Boronic Acid for ToF-SIMS and LDI-ToF Mass Spectrometry Imaging
Journal article, 2018

The analysis of small polar compounds with ToF-SIMS and MALDI-ToF-MS have been generally hindered by low detection sensitivity, poor ionization efficiency, ion suppression, analyte in-source fragmentation, and background spectral interferences from either a MALDI matrix and/or endogenous tissue components. Chemical derivatization has been a well-established strategy for improved mass spectrometric detection of many small molecular weight endogenous compounds in tissues. Here, we present a devised strategy to selectively derivatize and sensitively detect catecholamines with both secondary ion ejection and laser desorption ionization strategies, which are used in many imaging mass spectrometry (IMS) experiments. Chemical derivatization of catecholamines was performed by a reaction with a synthesized permanent pyridinium-cation-containing boronic acid molecule, 4-(N-methyl)pyridinium boronic acid, through boronate ester formation (boronic acid-diol reaction). The derivatization facilitates their sensitive detection with ToF-SIMS and LDI-ToF mass spectrometric techniques. 4-(N-Methyl)pyridinium boronic acid worked as a reactive matrix for catecholamines with LDI and improved the sensitivity of detection for both SIMS and LDI, while the isotopic abundances of the boron atom reflect a unique isotopic pattern for derivatized catecholamines in MS analysis. Finally, the devised strategy was applied, as a proof of concept, for on-tissue chemical derivatization and GCIB-ToF-SIMS (down to 3 μm per pixel spatial resolution) and LDI-ToF mass spectrometry imaging of dopamine, epinephrine, and norepinephrine in porcine adrenal gland tissue sections. MS/MS using collision-induced dissociation (CID)-ToF-ToF-SIMS was subsequently employed on the same tissue sections after SIMS and LDI mass spectrometry imaging experiments, which provided tandem MS information for the validation of the derivatized catecholamines in situ. This methodology can be a powerful approach for the selective and sensitive ionization/detection and spatial localization of diol-containing molecules such as aminols, vic-diols, saccharides, and glycans along with catecholamines in tissue sections with both SIMS and LDI/MALDI-MS techniques.


I. Kaya

University of Gothenburg

Sahlgrenska University Hospital

Steffen Brülls

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Physical Chemistry

Johan Dunevall

University of Gothenburg

Eva Jennische

University of Gothenburg

Stefan Lange

University of Gothenburg

Jerker Mårtensson

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry

Andrew Ewing

University of Gothenburg

Per Malmberg

University of Gothenburg

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry

John Fletcher

University of Gothenburg

Analytical Chemistry

0003-2700 (ISSN) 1520-6882 (eISSN)

Vol. 90 22 13580-13590

Molecular imaging at the synaptic level: the role of synaptic zinc in traumatic brain injury and neurodegenerative disease

Swedish Research Council (VR), 2016-01-01 -- 2019-12-31.

Subject Categories

Analytical Chemistry

Atom and Molecular Physics and Optics

Organic Chemistry


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