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可靠测定新的脂质过氧化化合物作为潜在的阿尔茨海默病早期生物标志物。

Reliable determination of new lipid peroxidation compounds as potential early Alzheimer Disease biomarkers.

机构信息

Neonatal Research Unit, Health Research Institute La Fe, Valencia, Spain; University of Valencia, Valencia, Spain.

Neonatal Research Unit, Health Research Institute La Fe, Valencia, Spain.

出版信息

Talanta. 2018 Jul 1;184:193-201. doi: 10.1016/j.talanta.2018.03.002. Epub 2018 Mar 6.

DOI:10.1016/j.talanta.2018.03.002
PMID:29674032
Abstract

Lipid peroxidation plays an important role in Alzheimer Disease, so corresponding metabolites found in urine samples could be potential biomarkers. The aim of this work is to develop a reliable ultra-performance liquid chromatography-tandem mass spectrometry analytical method to determine a new set of lipid peroxidation compounds in urine samples. Excellent sensitivity was achieved with limits of detection between 0.08 and 17 nmol L, which renders this method suitable to monitor analytes concentrations in real samples. The method's precision was satisfactory with coefficients of variation around 5-17% (intra-day) and 8-19% (inter-day). The accuracy of the method was assessed by analysis of spiked urine samples obtaining recoveries between 70% and 120% for most of the analytes. The utility of the described method was tested by analyzing urine samples from patients early diagnosed with mild cognitive impairment or mild dementia Alzheimer Disease following the clinical standard criteria. As preliminary results, some analytes (17(RS)-10-epi-SC-Δ-11-dihomo-IsoF, PGE) and total parameters (Neuroprostanes, Isoprostanes, Isofurans) show differences between the control and the clinical groups. So, these analytes could be potential early Alzheimer Disease biomarkers assessing the patients' pro-oxidant condition.

摘要

脂质过氧化在阿尔茨海默病中起着重要作用,因此尿液样本中发现的相应代谢物可能是潜在的生物标志物。本工作旨在开发一种可靠的超高效液相色谱-串联质谱分析方法,以确定尿液样本中一组新的脂质过氧化化合物。该方法的检测限在 0.08 至 17nmol·L 之间,具有优异的灵敏度,这使得该方法适用于监测实际样品中的分析物浓度。该方法的精密度令人满意,日内变异系数在 5-17%之间,日间变异系数在 8-19%之间。通过分析加标尿液样品来评估方法的准确性,大多数分析物的回收率在 70%-120%之间。通过分析根据临床标准标准早期诊断为轻度认知障碍或轻度阿尔茨海默病痴呆症的患者的尿液样本,测试了所描述方法的实用性。作为初步结果,一些分析物(17(RS)-10-epi-SC-Δ-11-dihomo-IsoF、PGE)和总参数(神经前列腺素、异前列腺素、异呋喃)在对照组和临床组之间存在差异。因此,这些分析物可能是评估患者促氧化剂状况的潜在早期阿尔茨海默病生物标志物。

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