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首页> 外文期刊>Journal of mass spectrometry: JMS >An optimized method for the detection and spatial distribution of aminoglycoside and vancomycin antibiotics in tissue sections by mass spectrometry imaging
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An optimized method for the detection and spatial distribution of aminoglycoside and vancomycin antibiotics in tissue sections by mass spectrometry imaging

机译：通过质谱成像对组织切片中氨基糖苷和万古霉素抗生素的检测和空间分布的优化方法

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摘要

Suboptimal antibiotic dosing has been identified as one of the key drivers in the development of multidrug-resistant (MDR) bacteria that have become a global health concern. Aminoglycosides and vancomycin are broad-spectrum antibiotics used to treat critically ill patients infected by a variety of MDR bacterial species. Resistance to these antibiotics is becoming more prevalent. In order to design proper antibiotic regimens that maximize efficacy and minimize the development of resistance, it is pivotal to obtain the in situ pharmacokinetic-pharmacodynamic profiles at the sites of infection. Mass spectrometry imaging (MSI) is the ideal technique to achieve this. Aminoglycosides, due to their structure, suffer from poor ionization efficiency. Additionally, ion suppression effects by endogenous molecules greatly inhibit the detection of aminoglycosides and vancomycin at therapeutic levels. In the current study, an optimized method was developed that enabled the detection of these antibiotics by MSI. Tissue spotting experiments demonstrated a 5-, 15-, 35-, and 54-fold increase in detection sensitivity in the washed samples for kanamycin, amikacin, streptomycin, and vancomycin, respectively. Tissue mimetic models were utilized to optimize the washing time and matrix additive concentration. These studies determined the improved limit of detection was 40 to 5 mu g/g of tissue for vancomycin and streptomycin, and 40 to 10 mu g/g of tissue for kanamycin and amikacin. The optimized protocol was applied to lung sections from mice dosed with therapeutic levels of kanamycin and vancomycin. The washing protocol enabled the first drug distribution investigations of aminoglycosides and vancomycin by MSI, paving the way for site-of-disease antibiotic penetration studies.
机译：次优抗生素剂量已被确定为多重耐药（MDR）细菌发展的关键驱动因素之一，这种细菌已成为全球健康问题。氨基糖苷和万古霉素是用于治疗多种耐多药细菌感染的危重病人的广谱抗生素。对这些抗生素的耐药性越来越普遍。为了设计适当的抗生素方案，最大限度地提高疗效，减少耐药性的发展，获得感染部位的原位药代动力学-药效学曲线至关重要。质谱成像（MSI）是实现这一目标的理想技术。氨基糖苷类由于其结构，电离效率很低。此外，内源性分子的离子抑制效应在治疗水平上极大地抑制了氨基糖苷和万古霉素的检测。在目前的研究中，开发了一种优化的方法，使MSI能够检测这些抗生素。组织斑点试验表明，在清洗后的样本中，卡那霉素、阿米卡星、链霉素和万古霉素的检测灵敏度分别提高了5倍、15倍、35倍和54倍。利用组织模拟模型优化洗涤时间和基质添加剂浓度。这些研究确定，万古霉素和链霉素的改良检测限为40至5μg/g组织，卡那霉素和阿米卡星的改良检测限为40至10μg/g组织。将优化方案应用于注射治疗水平卡那霉素和万古霉素的小鼠肺切片。清洗方案使MSI首次对氨基糖苷和万古霉素进行药物分布调查，为疾病部位抗生素渗透研究铺平了道路。

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