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Mass spectrometry imaging of levofloxacin distribution in TB-infected pulmonary lesions by MALDI-MSI and continuous liquid microjunction surface sampling

机译:MALDI-MSI和连续液体微结表面采样对左氧氟沙星在结核感染肺部病变中的分布进行质谱成像

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摘要

A multi-modal mass spectrometry imaging (MSI) and profiling approach has been applied to assess the partitioning of the anti-TB fluoroquinolone levofloxacin into pulmonary lesions. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and a commercial liquid microjunction surface sampling technology (LMJ-SSP), or flowprobe, have been used to both spatially profile and image drug distributions in lung tissue sections from TB-infected rabbits following oral administration of a single human-equivalent dose., Levofloxacin levels were highest at 6 h post-dose in normal lung, cellular granuloma, and necrotic caseum compartments. The drug accumulated in the cellular granuloma regions with lower amounts partitioning into central caseous compartments. Flowprobe imaging at 630 μm (limited by the probe tip diameter) enabled visualization of drug distribution into lesion compartments, including limited differentiation of relative drug abundance in cellular versus caseous regions of the lesions., MALDI-MSI analysis at 75 μm provided more detailed drug distribution, which clearly accumulated in the cellular region immediately surrounding the central caseum core. Imaging and profiling data acquired by flowprobe and MALDI-MSI were validated by quantitative LC/MS/MS analysis of lung and granuloma homogenates taken from the same animals., The results of the investigation show flowprobe imaging and sampling as a rapid and sensitive alternative to MALDI-MSI for profiling drug distributions into tissues when spatial resolution of data below the threshold of the probe diameter is not required.
机译:一种多模式质谱成像(MSI)和分析方法已应用于评估抗结核氟喹诺酮左氧氟沙星在肺部病变中的分配。基质辅助激光解吸电离质谱成像(MALDI-MSI)和商用液体微结表面采样技术(LMJ-SSP)或流探针已用于对结核感染的肺组织切片中的药物分布进行空间分布和成像在口服单人当量剂量的家兔后,左氧氟沙星的水平在正常肺部,细胞肉芽肿和坏死性干酪隔室中在给药后6 h最高。积聚在细胞肉芽肿区域中的药物较少,其分布在中央干酪样隔室中。 630μm的Flowprobe成像(受探针尖端直径的限制)可以观察到病变区域内药物的分布情况,包括在病变的细胞区域和干酪状区域中相对药物丰度的有限区分。75μm的MALDI-MSI分析提供了更详细的药物分布,明显聚集在紧靠中心酪蛋白核心的细胞区域。通过对来自同一动物的肺和肉芽肿匀浆的定量LC / MS / MS分析,验证了flowprobe和MALDI-MSI采集的成像和分析数据。研究结果表明,flowprobe成像和采样是快速,灵敏的替代方法。 MALDI-MSI用于在不需要低于探针直径阈值的数据的空间分辨率时将药物分布分析到组织中。

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