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

Abstract

BackgroundPhospholipids (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. ResultsA 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 noveltyA 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.