Bifunctional Ti4+-modified paper for selective extraction or removal of phospholipids and paper spray mass spectrometry for bioanalysis in urine and plasma

Wei Luo; Teris A van Beek; Bo Chen; Han Zuilhof; Gert Ij Salentijn

doi:10.1016/j.aca.2023.341673

Bifunctional Ti⁴⁺-modified paper for selective extraction or removal of phospholipids and paper spray mass spectrometry for bioanalysis in urine and plasma

Anal Chim Acta. 2023 Oct 16:1278:341673. doi: 10.1016/j.aca.2023.341673. Epub 2023 Jul 31.

Authors

Wei Luo¹, Teris A van Beek², Bo Chen³, Han Zuilhof⁴, Gert Ij Salentijn⁵

Affiliations

¹ Key Laboratory of Phytochemical R&D of Hunan Province and Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research of Ministry of Education, Hunan Normal University, Changsha, 410081, China; Laboratory of Organic Chemistry, Wageningen University, 6708, WE Wageningen, the Netherlands.
² Laboratory of Organic Chemistry, Wageningen University, 6708, WE Wageningen, the Netherlands.
³ Key Laboratory of Phytochemical R&D of Hunan Province and Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research of Ministry of Education, Hunan Normal University, Changsha, 410081, China. Electronic address: dr-chenpo@vip.sina.com.
⁴ Key Laboratory of Phytochemical R&D of Hunan Province and Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research of Ministry of Education, Hunan Normal University, Changsha, 410081, China; Laboratory of Organic Chemistry, Wageningen University, 6708, WE Wageningen, the Netherlands. Electronic address: Han.Zuilhof@wur.nl.
⁵ Laboratory of Organic Chemistry, Wageningen University, 6708, WE Wageningen, the Netherlands; Wageningen Food Safety Research (WFSR), Wageningen University & Research, 6700, AE Wageningen, the Netherlands. Electronic address: gert.salentijn@wur.nl.

PMID: 37709425
DOI: 10.1016/j.aca.2023.341673

Abstract

Background: Phospholipids (PLs) are major constituents of cell membranes, play important roles in cell proliferation and death, as well as in signal transduction, and therefore are relevant biomarkers for different pathologies. On the other hand, when the analysis of small compounds, such as therapeutics in blood is desired, then phospholipids are part of the matrix and cause serious interference during analysis. Currently, both the analysis and removal of PLs from biological samples are limited by extensive sample preparation and instrumental separation.

Results: A fast and simple quantitative Ti⁴⁺-modified paper spray tandem mass spectrometric (TiPS-MS/MS) method was established in urine, where the enrichment of phospholipids was achieved, as well as reduction of matrix effects (primarily caused by high salt content) that ultimately led to improved sensitivity and selectivity. The method could achieve a physiologically relevant limit of detection (0.01-0.03 μg mL^-1). Also, the usefulness of the Ti⁴⁺-modified paper was investigated in the opposite mode, namely for the selective removal of phospholipids from matrices such as plasma. Clonidine is used as model compound, as the detection of this compound is known to suffer from ion suppression by phospholipids. Compared with blank paper spray tandem mass spectrometry, the limit of detection could be improved from 0.3 μg mL^-1 to 0.03 μg mL^-1 by employing a Ti⁴⁺-modified paper on top of the spray tip to capture phospholipids from the sample.

Significance and novelty: A novel Ti⁴⁺-modified paper was developed to allow for rapid solid-phase extraction of phospholipids from urine or selective removal from plasma, followed by direct paper spray mass spectrometric detection as a fast and convenient sample preparation and analysis combination. The paper properties are based on the Ti⁴⁺ metal ion, which can selectively bind phosphate-containing compounds under acidic conditions, and its applicability was demonstrated in relevant biological matrices.

Keywords: Matrix effect; Paper modification; Paper spray mass spectrometry; Phospholipids; Selective enrichment.

MeSH terms

Body Fluids*
Phospholipids
Plasma
Tandem Mass Spectrometry*
Titanium

Substances

Titanium
Phospholipids