Advances in sample preparation and HPLC-MS/MS methods for determining amyloid-beta peptide in biological samples: a review

Autor(es)

de Souza, Israel Donizeti ; Queiroz, Maria Eugenia Costa

• Tipo de documento: Artigo Científico
• Fonte: ANALYTICAL AND BIOANALYTICAL CHEMISTRY; v. 415, n. 18, p. 19-pg., 2023-03-06.

Resumo

Alzheimer's disease (AD), a neurological disorder, is a major public health concern and the most common form of dementia. Its typical symptoms include memory loss, confusion, changes in personality, and cognitive impairment, which result in patients gradually losing independence. Over the last decades, some studies have focused on searching for effective biomarkers as early diagnostic indicators of AD. Amyloid-beta (A beta) peptides have been consolidated as reliable AD biomarkers and have been incorporated into modern diagnostic research criteria. However, quantitative analysis of A beta peptides in biological samples remains a challenge because both the sample and the physical-chemical properties of these peptides are complex. During clinical routine, A beta peptides are measured in the cerebrospinal fluid by immunoassays, but the availability of a specific antibody is critical-in some cases, an antibody may not exist, or its specificity may be inadequate, leading to low sensitivity and false results. HPLC-MS/MS has been reported as a sensitive and selective method for determining different fragments of A beta peptides in biological samples simultaneously. Developments in sample preparation techniques (preconcentration platforms) such as immunoprecipitation, 96-well plate SPME, online SPME, and fiber-in-tube SPME have enabled not only effective enrichment of A beta peptides present at trace levels in biological samples, but also efficient exclusion of interferents from the sample matrix (sample cleanup). This high extraction efficiency has provided MS platforms with higher sensitivity. Recently, methods affording LLOQ values as low as 5 pg mL(-1) have been reported. Such low LLOQ values are adequate for quantifying A beta peptides in complex matrixes including cerebrospinal fluid (CSF) and plasma samples. This review summarizes the advances in mass spectrometry (MS)-based methods for quantifying A beta peptides and covers the period 1992-2022. Important considerations regarding the development of the HPLC-MS/MS method such as the sample preparation step, optimization of the HPLC-MS/MS parameters, and matrix effects are described. Clinical applications, difficulties related to analysis of plasma samples, and future trends of these MS/MS-based methods are also discussed. (AU)

• 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
• 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: 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