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Toward Higher Sensitivity in Quantitative MALDI Imaging Mass Spectrometry of CNS Drugs Using a Nonpolar Matrix

Rzagalinski, Ignacy; Kovačević, Borislav; Hainz, Nadine; Meier, Carola; Tschernig, Thomas; Volmer, Dietrich A. (2018) Toward Higher Sensitivity in Quantitative MALDI Imaging Mass Spectrometry of CNS Drugs Using a Nonpolar Matrix. Analytical Chemistry, 90 (21). pp. 12592-12600. ISSN 0003-2700

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Tissue-specific ion suppression is an unavoidable matrix effect in MALDI mass spectrometry imaging (MALDI-MSI), the negative impact of which on precision and accuracy in quantitative MALDI-MSI can be reduced to some extent by applying isotope internal standards for normalization and matrix-matched calibration routines. The detection sensitivity still suffers, however, often resulting in significant loss of signal for the investigated analytes. An MSI application considerably affected by this phenomenon is the quantitative spatial analysis of central nervous system (CNS) drugs. Most of these drugs are low molecular weight, lipophilic compounds, which exhibit inefficient desorption and ionization during MALDI using conventional polar acidic matrices (CHCA, DHB). Here, we present the application of the (2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enylidene]malononitrile) matrix for high sensitivity imaging of CNS drugs in mouse brain sections. Since DCTB is usually described as an electron-transfer matrix, we provide a rationale (i.e., computational calculations of gas-phase proton affinity and ionization energy) for an additional proton-transfer ionization mechanism with this matrix. Furthermore, we compare the extent of signal suppression for five different CNS drugs when employing DCTB versus CHCA matrices. The results showed that the signal suppression was not only several times lower with DCTB than with CHCA but also depended on the specific tissue investigated. Finally, we present the application of DCTB and ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry to quantitative MALDI imaging of the anesthetic drug xylazine in mouse brain sections based on a linear matrix-matched calibration curve. DCTB afforded up to 100-fold signal intensity improvement over CHCA when comparing representative single MSI pixels and >440-fold improvement for the averaged mass spectrum of the adjacent tissue sections.

Item Type: Article
Additional Information: D.A.V. acknowledges research support by the German Research Foundation (FTICR-MS Facility, INST 256/356-1). The authors thank Tim Salbert (ACD/Laboratories) for the use of the Percepta software, Pascal Schorr (Humboldt University Berlin) for the rabbit brain preparations, Sylvia Kuhn (Saarland University) for SEM measurements, and Alexander Grissmer (Saarland University Medical Center) for staining and light microscopy experiments.
Uncontrolled Keywords: DCTB ; 2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enylidene]malononitrile ; mass spectrometry imaging ; MALDI ; FTICR ; CNS drugs ; xylazine
Subjects: NATURAL SCIENCES > Chemistry > Analytic Chemistry
Divisions: Division of Physical Chemistry
Depositing User: Borislav Kovačević
Date Deposited: 25 Nov 2019 08:01
DOI: 10.1021/acs.analchem.8b02740

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