Platform Technology and Science (PTS), Chemical Sciences, UK, GlaxoSmithKline (GSK), Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
Rapid Commun Mass Spectrom. 2014 May 15;28(9):995-1003. doi: 10.1002/rcm.6869.
The signal intensity of a given molecule across a tissue section when measured using mass spectrometry imaging (MSI) is prone to changes caused by the molecular heterogeneity across the surface of the tissue. Here we propose a strategy to investigate these effects using electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) on a single high-resolution mass spectrometry (HRMS) platform.
A rat was administered with a single inhaled dose of a compound and sacrificed 1 h after dosing. Sections were prepared from the excised frozen lung and analysed using MALDI, liquid extraction surface analysis (LESA) nano-ESI-MS and nano-ESI liquid chromatography (LC)/MS. The ESI and MALDI ion sources were mounted either side of the ion transfer system of the same Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer.
MALDI MSI clearly demonstrated widespread distribution of the dosed molecule throughout the lung, with the exception of a non-lung section of tissue on the same sample surface. Comparison of the lipid signals across the sample indicated a change in signal between the lung and the adipose tissue present on the same section. Use of ESI and MALDI, with and without an internal standard, supported the evaluation of changes in the signal of the dosed molecule across the tissue section.
The results demonstrate the successful application of a dual ion source HRMS system to the systematic evaluation of data from MALDI MSI, used to determine the distribution of an inhaled drug in the lung. The system discussed is of great utility in investigating the effects of ion suppression and evaluating the quantitative and qualitative nature of the MSI data.
当使用质谱成像 (MSI) 测量组织切片中给定分子的信号强度时，它容易受到组织表面分子异质性引起的变化的影响。在这里，我们提出了一种使用电喷雾电离 (ESI) 和基质辅助激光解吸/电离 (MALDI) 在单个高分辨率质谱 (HRMS) 平台上研究这些效应的策略。
给大鼠单次吸入剂量的化合物，然后在给药后 1 小时处死。从切除的冷冻肺中制备切片，并使用 MALDI、液体提取表面分析 (LESA) 纳米 ESI-MS 和纳米 ESI 液相色谱 (LC)/MS 进行分析。ESI 和 MALDI 离子源安装在同一傅里叶变换离子回旋共振 (FT-ICR) 质谱仪的离子传输系统的两侧。
MALDI MSI 清楚地表明，除了同一样品表面的非肺组织部分外，被给药的分子广泛分布在整个肺部。比较样品中的脂质信号表明，信号在肺和同一部位的脂肪组织之间发生了变化。使用 ESI 和 MALDI，以及使用和不使用内标，支持了对组织切片中被给药分子信号的变化进行评估。
结果表明，双离子源 HRMS 系统成功应用于 MALDI MSI 数据的系统评估，用于确定吸入药物在肺部的分布。所讨论的系统在研究离子抑制的影响和评估 MSI 数据的定量和定性性质方面非常有用。
