Direct coupling of fiber-in-tube solid-phase microextraction with tandem mass spectrometry to determine amyloid beta peptides as biomarkers for Alzheimer's disease in cerebrospinal fluid samples
Direct coupling of fiber-in-tube solid-phase microextraction with tandem mass spectrometry to determine amyloid beta peptides as biomarkers for Alzheimer's disease in cerebrospinal fluid samples
复制标题
管内纤维固相微萃取与串联质谱直接耦合以确定淀粉样β肽作为脑脊液样本中阿尔茨海默病的生物标志物
DOI：
10.1016/j.talanta.2022.124186
复制
发表时间：
2023
期刊：
影响因子：
6.1
通讯作者：
Queiroz, Maria Eugênia
中科院分区：
文献类型：
--
作者：
Souza, Israel D.;Anderson, Jared L.;Tumas, Vitor;Queiroz, Maria Eugênia
目前神经系统疾病的研究工作集中在识别新的生物标志物，以帮助诊断，提供准确的预后信息，并监测疾病进展。本研究提出了一种可靠的方法，直接耦合管中纤维固相微萃取串联质谱测定淀粉样β肽（Aβ38，Aβ40和Aβ42）作为生物标志物的阿尔茨海默病在脑脊液（CSF）样本。为了获得生物相容性的管内纤维SPME毛细管，PEEK管段纵向填充有细纤维[涂有两性离子聚合物离子液体的镍钛合金丝]，以作为选择性提取介质。该方法将分析物提取/富集和样品净化（排除干扰物）集成为一个步骤。该方法具有较低的定量限（LLOQ：Aβ38为0.2 ng mL− 1，Aβ40和Aβ42为0.1 ng mL− 1）、高精密度（CV低于11.6%）和高准确度（相对标准偏差低于15.1%）。该方法已成功应用于AD患者（n = 8）和健康志愿者（n = 10）脑脊液中Aβ肽的测定。结果显示，AD患者脑脊液中Aβ42水平显著低于健康对照组（p< 0.05）。根据ROC分析结果，Aβ42/Aβ40比值（AUC = 0.950，p < 0.01; 95%）在区分AD患者和健康对照方面的表现显著优于单独的Aβ42（AUC = 0.913，p < 0.01; 95%），并表现出更好的AD诊断能力。本研究的创新之处不仅在于评估Aβ肽作为AD生物标志物的价值，而且还在于证明了纤维-管SPME与MS/MS的直接线性耦合作为一种定量的高通量生物分析方法。
Current research efforts at neurological diseases have focused on identifying novel biomarkers to aid in diagnosis, to provide accurate prognostic information, and to monitor disease progression. This study presents the direct coupling offiber-in-tubesolid-phase microextraction totandemmass spectrometry as a reliable method to determine amyloid beta peptides (Aβ38, Aβ40, and Aβ42) as biomarkers for Alzheimer's disease in cerebrospinal fluid (CSF) samples. To obtain the biocompatiblefiber-in-tubeSPME capillary, a PEEK tube segment was longitudinally packed with fine fibers [nitinol wires coated with a zwitterionic polymeric ionic liquid], to act as selective extraction medium. Thefiber-in-tubeSPME–MS/MS method integrated analyte extraction/enrichment and sample cleanup (exclusion of interferents) into one step. The method provided lower limits of quantification (LLOQ: 0.2 ng mL−1for Aβ38 and 0.1 ng mL−1for Aβ40 and Aβ42), high precision (CV lower than 11.6%), and high accuracy (relative standard deviation lower than 15.1%). This method was successfully applied to determine Aβ peptides in CSF samples obtained from AD patients (n = 8) and controls (healthy volunteers, n = 10). Results showed that Aβ42 levels in the CSF samples obtained from AD patients were significantly lower compared to healthy controls (p< 0.05). On the basis of the ROC analysis results, the Aβ42/Aβ40 ratio (AUC = 0.950, p < 0.01; 95%) performed significantly better than Aβ42 alone (AUC = 0.913, p < 0.01; 95%) in discriminating between AD patients and healthy controls and presented better diagnostic ability for AD. The novelties of this study are not only related to evaluating Aβ peptides as AD biomarkers, but also to demonstrating directonlinecoupling offiber-in-tubeSPME with MS/MS as a quantitative high-throughput method for bioanalysis.