关键词: Budesonide Ferulic acid Girard reagent Mass spectrometry imaging On-tissue derivatization Pulmonary drug distribution

Mesh : Animals Budesonide / administration & dosage analysis pharmacokinetics Glucocorticoids / administration & dosage analysis pharmacokinetics Indicators and Reagents Lung / metabolism Rabbits Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods Steroids / administration & dosage analysis pharmacokinetics

来  源:   DOI:10.1007/s00216-021-03393-6   PDF(Sci-hub)   PDF(Pubmed)

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:
皮质类固醇如布地奈德可有效减少不同器官的局部炎症过程。布地奈德在呼吸系统疾病中的治疗用途,比如哮喘,慢性阻塞性肺疾病,过敏性鼻炎是众所周知的。然而,布地奈德的肺部分布尚不清楚,主要是由于在不添加标记的情况下难以追踪肺样品中的分子。在本文中,我们提出了一种基质辅助激光解吸/电离质谱成像方案,该方案可用于观察表面活性剂耗尽的成年兔的布地奈德的肺部分布.考虑到布地奈德不易被MALDI电离,我们开发了一种使用Girard试剂P的组织上衍生方法,然后将阿魏酸沉积为MALDI基质。有趣的是,这种样品制备方案的结果是一个非常有效的策略,以提高敏感性不仅布地奈德,而且其他皮质类固醇,使我们能够追踪其分布并量化肺部样本中的药物。
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