Enhanced Sensitivity Using MALDI Imaging Coupled with Laser Postionization (MALDI-2) for Pharmaceutical Research
Enhanced Sensitivity Using MALDI Imaging Coupled with Laser Postionization (MALDI-2) for Pharmaceutical Research
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DOI：
10.1021/acs.analchem.9b02495
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发表时间：
2019-08-20
影响因子：
7.4
通讯作者：
Heeren, Ron M. A.
中科院分区：
文献类型：
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作者：
Barre, Florian P. Y.;Paine, Martin R. L.;Heeren, Ron M. A.
药物及其代谢产物分布的可视化是基质辅助激光解吸/电离质谱成像（MALDI-MSI）在药物研究中的关键新兴应用领域之一。给定的MALDI-MSI实验的成功最终由感兴趣的化合物的电离效率决定，在许多情况下，电离效率太低而不能在相关浓度下进行检测。在这项工作中，我们已经采取措施来解决这一挑战，通过第一次应用激光定位与MALDI（所谓的MALDI-2）的药物化合物的分析和成像。我们证明，MALDI-2增加了信号强度为7的10种药物化合物分析了高达2个数量级相比，传统的MALDI分析。这种灵敏度的增加使得能够使用MALDI-2分布药物化合物，而使用常规MALDI从组织获得很少或没有信号。这项工作展示了MALDI-2-MSI在药物研究和药物开发中的巨大潜力，并为扩大MSI的应用领域提供了一个有价值的工具。最后，在努力了解电离机制，我们提供了第一个证据，优先形成的[M + H]（+）离子与MALDI-2没有明显的相关性与气相质子亲和力值的分析物分子，这表明，与MALDI，发生复杂的，但尚未阐明电离现象。
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.