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

Alzheimer disease (AD) is a neurodegenerative disorder characterized by extracellular accumulation of amyloid-beta peptide (A beta) in the brain interstitium. Human serum albumin (HSA) highly binds to A beta in blood plasma and is thought to inhibit plaque formation in peripheral tissue. Thus, the evaluation of albumin binding to A beta is an important key to understand the dynamics of these molecules in the biological system of patients with AD. In this work, a fiber-in-tube solid-phase microextraction (fiber-in-tube SPME) and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to estimate A beta fraction binding to HSA in cerebrospinal fluid (CSF) and plasma samples. Crosslinked zwitterionic polymeric ionic liquid (zwitterionic PIL)-coated nitinol wires were developed and packed into a polyether ether ketone (PEEK) capillary for a fiber-in-tube SPME and UHPLC-MS/MS method. Zwitterionic PIL sorbent was synthetized from 1-vinyl-3-(butanesulfonate)imidazolium ([VIm(+)C(4)SO(3)(-)]) and 1,12-di(3-vinylimidazolium)dodecane dibromide ([(VIm)(2)C-12](2)[Br]) monomers by in-situ thermally-initiated polymerization. Morphological characterization by scanning electron microscopy (SEM) and atomic force microscopy (AFM) revealed a decrease in the surface roughness of the nitinol wires from similar to 17 nm to 1 nm after the in-situ polymerization. The zwitterionic PIL sorbent selectively preconcentrates A beta through a two-pronged interaction mechanism. The fiber-in-tube SPME and UHPLC-MS/MS method presented lower limits of quantification (LLOQ) of 0.4 ng mL(-1) for A beta 38 and 0.3 ng mL(-1) for A beta 40 and A beta 42, a linear range from LLOQ values to 15 ng mL(-1) with coefficients of determination higher than 0.99, precision with coefficient of variation (CV) values ranging from 2.1 to 7.3% and accuracy with relative standard deviation (RSD) values from -0.3 to 7.4. This method was successfully applied to evaluate the binding of HSA to A beta in cerebrospinal fluid (CSF) and plasma samples. (C) 2021 Elsevier B.V. All rights reserved.