Simultaneous optimization of paper spray substrates and solvents for hydrophilic and hydrophobic molecules

Abstract

Paper spray mass spectrometry is an ambient ionization technique capable of the direct ionization of analyte from a bio-fluid spot on a paper substrate. Different solvents and types of paper can have different interactions with the analytes of interest; therefore, they can significantly impact the analyte signal and the assay as a whole. In this study, we examined the effects of substrate-solvent composition on signal intensity, blank signal intensity, and signal-to-blank ratio for a variety of pharmaceutical drugs, illicit drugs, chemical warfare agent (CWA) simulants, and CWA hydrolysis products. The analytes were prepared either neat or spiked into human plasma and deposited on a variety of modified paper substrates. Extraction occurred with a range of different solvents. Optimizing the substrate-solvent combination improved the signal-to-blank ratio for all compounds ranging from 1 to 7,964 factor improvement, with the substrate providing a more impactful improvement. Aprotic solvents, such as tetrahydrofuran and ethyl acetate, tended to produce optimal signal-to-blank ratios, while carbon sputtered and glass fiber substrates were the top paper substrates. The research presented herein illustrates the need for systematic optimization of substrate and spray solvent combinations to achieve the best detection limits for paper spray analysis.