Fiber-in-tube SPME-CapLC-MS/MS method to determine A β peptides in cerebrospinal fluid obtained from Alzheimer ' s patients

Autor(es)

de Souza, Israel Donizeti ; Lancas, Fernando M. ; Hallak, Jaime E. Cecilio ; Queiroz, Maria E. Costa

• Tipo de documento: Artigo Científico
• Fonte: Journal of Chromatography A; v. 1723, p. 7-pg., 2024-04-19.

Resumo

Mass spectrometry is characterized by its high sensitivity, ability to measure very low analyte concentrations, specificity to distinguish between closely related compounds, availability to generate high-throughput methods for screening, and high multiplexing capacity. This technique has been used as a platform to analyze fluid biomarkers for Alzheimer 's disease. However, more effective sample preparation procedures, preferably antibody-independent, and more automated mass spectrometry platforms with improved sensitivity, chromatographic separation, and high throughput are needed for this purpose. This short communication discusses the development of a fiber-in-tube SPME-CapLC-MS/MS method to determine A beta peptides in cerebrospinal fluid obtained from Alzheimer 's disease patients. To obtain the fiber-in-tube SPME capillary, we longitudinally packed 22 nitinol fibers coated with a zwitterionic polymeric ionic liquid into the same length of the PEEK tube. In addition, this communication compares this fiber-in-tube SPME method with the conventional HPLC scale (HPLCMS/MS) and when directly coupled to CapESI-MS/MS without chromatographic separation, and, as a case study, discusses the benefits and challenges inherent in miniaturizing the flow scale of the sample preparation technique ( fiber-in-tube SPME) to the CapLC-MS/MS system. Fiber-in-tube SPME-CapLC-MS/MS provided LLOQ ranging from 0.09 to 0.10 ng mL -1 , accuracy ranging from 91 to 117 % (recovery), and reproducibility of less than 18 % (RSD). Analysis of the cerebrospinal fluid samples obtained from Alzheimer 's disease patients evidenced that the method is robust. At the capillary scale (10 mu L min -1 ), this innovative method presented higher analytical sensitivity than the conventional HPLC-MS/MS scale. Although fiber-in-tube SPME directly coupled to CapESI-MS/MS offers advantages in terms of high throughput, the sample was dispersed and non-quantitatively desorbed from the capillary at low flow rate. These results highlighted that chromatographic separation is important to decrease the matrix effect and to achieve higher detectability, which is indispensable for bioanalysis. (AU)

• Processo FAPESP: 20/00126-8 - Desenvolvimento de métodos de microextração hifenados à LC-MS/MS ou diretamente à MS/MS para a determinação de biomarcadores em amostras biológicas de pacientes ou de ratos com doenças neurodegenerativas
• Beneficiário: Maria Eugênia Queiroz Nassur
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/21984-0 - EMU concedido no processo 17/02147-0: sistema de nano-cromatografia líquida de alta eficiência hifenada a espectrometria de massas com ionização por elétrons e analisador quadrupolar (EI-Q (MS)) - nano-LC-EI-MS
• Beneficiário: Fernando Mauro Lanças
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 17/21985-6 - EMU concedido no processo 17/02147-0: sistema de nano/micro-cromatografia líquida de alta eficiência hifenada a espectrometria de massas com ionização por electrospray e analisador sequencial quadrupolar (ESI-QqQ (MS/MS)) - nano/µ-LC-ESI-MS/MS
• Beneficiário: Fernando Mauro Lanças
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 19/19485-0 - Desenvolvimento de fibras de nitinol revestidas com líquidos iônicos poliméricos zwiteriônicos para a determinação de beta-amilóides em amostras de plasma de pacientes com doença de Alzheimer através do acoplamento direto fiber-in-tube SPME e MS/MS
• Beneficiário: Israel Donizeti de Souza
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/02147-0 - Cromatografia líquida em uma gota e seu acoplamento com espectrometria de massas: estratégias instrumentais, desenvolvimento de materiais, automatização e aplicações analíticas
• Beneficiário: Fernando Mauro Lanças
• Modalidade de apoio: Auxílio à Pesquisa - Temático