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采用 MALDI 质谱成像技术检测类甾族化合物的样品制备策略:以布地奈德为例的肺部分布研究。

Sample preparation strategy for the detection of steroid-like compounds using MALDI mass spectrometry imaging: pulmonary distribution of budesonide as a case study.

机构信息

Mass Spectrometry Center, Department of Health Sciences, University of Florence, Viale G. Pieraccini 6, 50139, Florence, Italy.

Unit of Computational Biology, Research and Innovation Centre, Fondazione E. Mach, S. Michele all'Adige, 38198, Trento, Italy.

出版信息

Anal Bioanal Chem. 2021 Jul;413(16):4363-4371. doi: 10.1007/s00216-021-03393-6. Epub 2021 May 17.

DOI:10.1007/s00216-021-03393-6
PMID:34002273
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8222037/
Abstract

Corticosteroids as budesonide can be effective in reducing topic inflammation processes in different organs. Therapeutic use of budesonide in respiratory diseases, like asthma, chronic obstructive pulmonary disease, and allergic rhinitis is well known. However, the pulmonary distribution of budesonide is not well understood, mainly due to the difficulties in tracing the molecule in lung samples without the addition of a label. In this paper, we present a matrix-assisted laser desorption/ionization mass spectrometry imaging protocol that can be used to visualize the pulmonary distribution of budesonide administered to a surfactant-depleted adult rabbit. Considering that budesonide is not easily ionized by MALDI, we developed an on-tissue derivatization method with Girard's reagent P followed by ferulic acid deposition as MALDI matrix. Interestingly, this sample preparation protocol results as a very effective strategy to raise the sensitivity towards not only budesonide but also other corticosteroids, allowing us to track its distribution and quantify the drug inside lung samples.

摘要

倍他米松等皮质类固醇可以有效减轻不同器官的局部炎症反应。倍他米松在治疗哮喘、慢性阻塞性肺疾病和过敏性鼻炎等呼吸道疾病方面已有广泛应用。然而,人们对倍他米松在肺部的分布情况了解甚少,这主要是因为在不添加标记的情况下,很难追踪肺部样本中的分子。本文提出了一种基质辅助激光解吸/电离质谱成像方案,可用于可视化给予去表面活性剂成年兔的倍他米松在肺部的分布。鉴于倍他米松不易被 MALDI 电离,我们开发了一种组织内衍生化方法,使用 Girard's 试剂 P 进行衍生化,然后用阿魏酸作为 MALDI 基质进行沉积。有趣的是,这种样品制备方案是一种非常有效的策略,不仅可以提高倍他米松的灵敏度,还可以提高其他皮质类固醇的灵敏度,使我们能够追踪其分布并定量检测肺部样本中的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97cd/8222037/e50c19d18578/216_2021_3393_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97cd/8222037/777022179f25/216_2021_3393_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97cd/8222037/c9edde90b06b/216_2021_3393_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97cd/8222037/f9d0fa3eccf2/216_2021_3393_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97cd/8222037/e50c19d18578/216_2021_3393_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97cd/8222037/777022179f25/216_2021_3393_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97cd/8222037/c9edde90b06b/216_2021_3393_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97cd/8222037/f9d0fa3eccf2/216_2021_3393_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97cd/8222037/e50c19d18578/216_2021_3393_Fig4_HTML.jpg

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