Enhanced Sensitivity Using MALDI Imaging Coupled with Laser Postionization (MALDI-2) for Pharmaceutical Research

被引:78
作者
Barre, Florian P. Y. [1 ]
Paine, Martin R. L. [1 ]
Flinders, Bryn [1 ]
Trevitt, Adam J. [2 ]
Kelly, Patrick D. [2 ]
Ait-Belkacem, Rima [3 ]
Garcia, Joao P. [4 ]
Creemers, Laura B. [4 ]
Stauber, Jonathan [3 ]
Vreeken, Rob J. [1 ,5 ]
Cillero-Pastor, Berta [1 ]
Ellis, Shane R. [1 ]
Heeren, Ron M. A. [1 ]
机构
[1] Maastricht Univ, Maastricht MultiModal Mol Imaging Inst M4I, Div Imaging Mass Spectrometry, Univ Singel 50, NL-6229 ER Maastricht, Netherlands
[2] Univ Wollongong, Sch Chem, Wollongong, NSW, Australia
[3] ImaBiotech, Loos, France
[4] Univ Med Ctr UMC Utrecht, Dept Orthoped, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands
[5] Janssen Res & Dev, Discovery Sci, Beerse, Belgium
关键词
DESORPTION IONIZATION; ELECTROSPRAY-IONIZATION; ION FORMATION; TISSUE; DERIVATIZATION; CELLS; RESOLUTION; MOLECULES; MECHANISM; PRESSURE;
D O I
10.1021/acs.analchem.9b02495
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Visualizing the distributions of drugs and their metabolites is one of the key emerging application areas of matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) within pharmaceutical research. The success of a given MALDI-MSI experiment is ultimately determined by the ionization efficiency of the compounds of interest, which in many cases are too low to enable detection at relevant concentrations. In this work we have taken steps to address this challenge via the first application of laser-postionisation coupled with MALDI (so-called MALDI-2) to the analysis and imaging of pharmaceutical compounds. We demonstrate that MALDI-2 increased the signal intensities for 7 out of the 10 drug compounds analyzed by up to 2 orders of magnitude compared to conventional MALDI analysis. This gain in sensitivity enabled the distributions of drug compounds using MALDI-2, whereas little-to-no signal from tissue was obtained using conventional MALDI. This work demonstrates the vast potential of MALDI-2-MSI in pharmaceutical research and drug development and provides a valuable tool to broaden the application areas of MSI. Finally, in an effort to understand the ionization mechanism, we provide the first evidence that the preferential formation of [M + H](+) ions with MALDI-2 has no obvious correlation with the gas-phase proton affinity values of the analyte molecules, suggesting, as with MALDI, the occurrence of complex and yet to be elucidated ionization phenomena.
引用
收藏
页码:10840 / 10848
页数:9
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