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

Author(s)

Souza, Israel D. ; Anderson, Jared L. ; Tumas, Vitor ; Queiroz, Maria Eugenia C.

• Document type: Journal article
• Source: Talanta; v. 254, p. 8-pg., 2023-03-01.

Abstract

Current research efforts at neurological diseases have focused on identifying novel biomarkers to aid in diag-nosis, to provide accurate prognostic information, and to monitor disease progression. This study presents the direct coupling of fiber-in-tube solid-phase microextraction to tandem mass spectrometry as a reliable method to determine amyloid beta peptides (A beta 38, A beta 40, and A beta 42) as biomarkers for Alzheimer's disease in cerebrospinal fluid (CSF) samples. To obtain the biocompatible fiber-in-tube SPME capillary, a PEEK tube segment was longi-tudinally packed with fine fibers [nitinol wires coated with a zwitterionic polymeric ionic liquid], to act as se-lective extraction medium. The fiber-in-tube SPME-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-1 for A beta 38 and 0.1 ng mL-1 for A beta 40 and A beta 42), high precision (CV lower than 11.6%), and high accuracy (relative standard deviation lower than 15.1%). This method was successfully applied to deter-mine A beta peptides in CSF samples obtained from AD patients (n = 8) and controls (healthy volunteers, n = 10). Results showed that A beta 42 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 A beta 42/A beta 40 ratio (AUC = 0.950, p < 0.01; 95%) performed significantly better than A beta 42 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 A beta peptides as AD biomarkers, but also to demonstrating direct online coupling of fiber-in-tube SPME with MS/MS as a quantitative high-throughput method for bioanalysis. (AU)

• FAPESP's process: 19/19485-0 - Development of nitinol fiber chemically coated with zwitterionic polymeric ionic liquids for determination of beta-amyloids in plasma samples from patients with Alzheimer's disease by direct coupling fiber-in-tube SPME and MS/MS
• Grantee: Israel Donizeti de Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/00126-8 - Development of the methods of the microextraction hyphenated with LC-MS/MS or directly to MS/MS for the determination of biomarkers in biological samples of patient or rats with neurodegenerative diseases
• Grantee: Maria Eugênia Queiroz Nassur
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/02147-0 - Single drop chromatography and its coupling to mass spectrometry: instrumental strategies, development of materials, automation and analytical applications
• Grantee: Fernando Mauro Lanças
• Support Opportunities: Research Projects - Thematic Grants