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

• Grant number: 20/00126-8
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2020 - June 30, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal Investigator: Maria Eugênia Queiroz Nassur
• Grantee: Maria Eugênia Queiroz Nassur
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: José Alexandre de Souza Crippa ; Vitor Tumas

Abstract

The conclusive diagnosis of neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD), has been predominantly clinical and, in these cases, the neurodegeneration is already installed in the patient's brain. Therefore, efforts have been made to identify molecular biomarkers for early diagnosis and monitoring these neurodegenerations progression. High performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has been considered a reference analytical technique for the determination of biomarkers in biological fluids. Due to complexity of biological fluids, LC-MS/MS methods require a sample preparation step to exclude the biological matrix macromolecules and to concentrate the analytes (trace levels). The sample preparation techniques have been simplified, miniaturized (lower sample and organic solvent consumption), and/or hyphenation with chromatographic systems, automation (high-throughput performance). In this context, we can highlight the salting-out assisted liquid-liquid microextraction (microSALLE) and in-tube microextraction (in-tube SPME) hyphenated with LC-MS/MS. The development of capillaries with innovative bifunctional stationary phase for in-tube SPME, such as organic monolithic phases combined with restricted access materials (RAM) and polymerizable zwitterionic ionic liquids (ZILs) has allowed selective pre-concentration of the analytes. In this project, for the evaluation of potential biomarkers for DA, the following methods will be developed for the determination of AD biomarkers in plasma and cerebrospinal fluid samples: (a) in-tube SPME-LC-MS/MS using a organic monolithic capillary with sulfonic groups with RAM covering for the determination of ²-amyloid peptides, (b) in-tube SPME-MS/MS using a polyester(ether)ketone (PEEK) capillary packed with nitinol fibers (SPME support) coated with ZILs for determination ²-amyloid peptides and (c) in-tube SPME-LC-MS/MS using a organic monolithic capillary with cation-exchange groups with RAM covering for determination of homocysteine and homocysteic acid. For the evaluation of PD biomarkers, the microSALLE/LC-MS/MS method will be developed for the determination of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in parkinsonism-induced rats treated or not with levodopa (L-Dopa). Therefore, in agreement with the state-of-the-art of the miniaturized sample preparation and separation techniques, this project is noteworthy in the field of neuroscience. (AU)

Scientific publications

(13)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GRECCO, CAROLINE FERNANDES; DE SOUZA, ISRAEL DONIZETI; OLIVEIRA, IGOR GUSTAVO CARVALHO; QUEIROZ, MARIA EUGENIA COSTA. In-Tube Solid-Phase Microextraction Directly Coupled to Mass Spectrometric Systems: A Review. SEPARATIONS, v. 9, n. 12, p. 19-pg., 2022-12-01. (17/02147-0, 19/19485-0, 20/00126-8, 20/06526-8, 19/04386-7)

GRECCO, CAROLINE FERNANDES; TUMAS, VITOR; HALLAK, JAIME EDUARDO CECILIO; QUEIROZ, MARIA EUGENIA COSTA. In-tube solid-phase microextraction (sulfopropyl methacrylate-co-ethylene glycol dimethacrylate monolithic capillary) coupled to LC-MS/MS to determine beta amyloid peptides in Alzheimer's cerebrospinal fluid samples. SEPARATION SCIENCE PLUS, v. N/A, p. 12-pg., 2023-08-07. (17/02147-0, 20/00126-8, 19/04386-7)

CAROLINE F. GRECCO; EDUARDO JOSÉ CREVELIN; VITOR TUMAS; JAIME EDUARDO C. HALLAK; MARIA EUGÊNIA C. QUEIROZ. Disposable Pipette Extraction Followed by Direct MS/MS Analysis of Beta Amyloid Peptides (Aß38, Aß40, and Aβ42) in Cerebrospinal Fluid Samples. Journal of the Brazilian Chemical Society, v. 36, n. 1, 2024-06-17. (17/02147-0, 20/00126-8, 19/04386-7)

SOUZA, ISRAEL D.; OLIVEIRA, IGOR G. C.; QUEIROZ, MARIA EUGENIA C.. Innovative extraction materials for fiber-in-tube solid phase microextraction: A review. Analytica Chimica Acta, v. 1165, JUN 22 2021. (20/00126-8, 18/06068-0, 17/02147-0, 19/19485-0)

DE SOUZA, ISRAEL DONIZETI; QUEIROZ, MARIA EUGENIA COSTA. Advances in sample preparation and HPLC-MS/MS methods for determining amyloid-beta peptide in biological samples: a review. ANALYTICAL AND BIOANALYTICAL CHEMISTRY, v. 415, n. 18, p. 19-pg., 2023-03-06. (17/02147-0, 19/19485-0, 20/00126-8)

SOUZA, ISRAEL D.; ANDERSON, JARED L.; TUMAS, VITOR; QUEIROZ, MARIA EUGENIA C.. 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. Talanta, v. 254, p. 8-pg., 2023-03-01. (19/19485-0, 20/00126-8, 17/02147-0)

CRUZ, JONAS CARNEIRO; DE SOUZA, ISRAEL DONIZETI; LANCAS, FERNANDO MAURO; COSTA QUEIROZ, MARIA EUGENIA. Current advances and applications of online sample preparation techniques for miniaturized liquid chromatography systems. Journal of Chromatography A, v. 1668, p. 16-pg., 2022-04-12. (19/19485-0, 17/02147-0, 20/00126-8)

SOUZA, ISRAEL D.; ANDERSON, JARED L.; QUEIROZ, MARIA EUGENIA C.. Crosslinked zwitterionic polymeric ionic liquid-functionalized nitinol wires for fiber-in-tube solid-phase microextraction and UHPLC-MS/MS as an amyloid beta peptide binding protein assay in biological fluids. Analytica Chimica Acta, v. 1193, FEB 8 2022. (17/02147-0, 19/19485-0, 20/00126-8)

CRUZ, JONAS CARNEIRO; DE SOUZA, ISRAEL DONIZETI; GRECCO, CAROLINE FERNANDES; FIGUEIREDO, EDUARDO COSTA; QUEIROZ, MARIA EUGENIA COSTA. Recent advances in column switching high-performance liquid chromatography for bioanalysis. SUSTAINABLE CHEMISTRY AND PHARMACY, v. 21, JUN 2021. (19/19485-0, 19/04386-7, 20/00126-8, 17/02147-0)

GRECCO, CAROLINE FERNANDES; DE SOUZA, ISRAEL DONIZETI; QUEIROZ, MARIA EUGENIA COSTA. Novel materials as capillary coatings for in-tube solid-phase microextraction for bioanalysis. JOURNAL OF SEPARATION SCIENCE, v. 44, n. 8, p. 1662-1693, APR 2021. (17/02147-0, 20/00126-8, 19/04386-7, 19/19485-0)

CARVALHO OLIVEIRA, IGOR GUSTAVO; DE SOUZA, ISRAEL DONIZETI; DO NASCIMENTO, GLAUCE CRIVELARO; DEL BEL, ELAINE; COSTA QUEIROZ, MARIA EUGENIA. In-tube solid-phase microextraction directly coupled to tandem mass spectrometry for anandamide and 2-arachidonoylglycerol determination in rat brain samples from an animal model of Parkinson's disease. Journal of Chromatography A, v. 1636, JAN 11 2021. (19/19485-0, 18/06068-0, 20/00126-8, 14/50891-1)

COSTA QUEIROZ, MARIA EUGENIA; DE SOUZA, ISRAEL DONIZETI; DE OLIVEIRA, IGOR GUSTAVO; GRECCO, CAROLINE FERNANDES. In vivo solid phase microextraction for bioanalysis. TRAC-TRENDS IN ANALYTICAL CHEMISTRY, v. 153, p. 18-pg., 2022-05-04. (20/06526-8, 17/02147-0, 19/04386-7, 19/19485-0, 20/00126-8)

PINTO, MANIA A. L.; DE SOUZA, ISRAEL D.; MIRANDA, LUIS FELIPPE C.; QUEIROZ, MARIA EUGENIA C.. A New Molecularly Imprinted Polymer for In-Tube SPME/UHPLC-MS/MS of Anandamide in Plasma Samples. Journal of the Brazilian Chemical Society, v. N/A, p. 9-pg., 2023-05-16. (13/03808-9, 15/07619-1, 17/02147-0, 20/00126-8, 19/19485-0)