Sub-ppt Mass Spectrometric Detection of Therapeutic Drugs in Complex Biological Matrixes Using Polystyrene-Microsphere-Coated Paper Spray

Abstract

Polystyrene (PS) is a class of polymer materials that offers great potential for various applications. However, the applications of PS microspheres in paper spray mass spectrometry are largely underexplored. Herein we prepared a series of PS microspheres via a simple dispersion polymerization and then used them as coating materials for paper spray mass spectrometry (MS) in high-sensitivity analysis of various therapeutic drugs in complex biological matrixes. In the preparation of PS-coated papers, the coating method was found playing a key role in determining the performance of the resulting paper substrate in addition to other parameters (e.g., starch type and amount, PS coating amount, and spray solvent). We also found that as a solvent was applied on PS-coated paper for paper spray, the analytes of interest would be first extracted out and then moved to the tip of paper triangle for spray along with the applied solvent. In the process, the surface energy of PS particles had a strong impact on the desorption performance of analytes from PS-coated paper substrate, and the PS with a high surface energy favored the elution of analytes to allow a high MS sensitivity. When the prepared PS coated paper was used as a substrate for paper spray, it gave high sensitivity in analysis of therapeutic drugs in various biological matrixes such as whole blood, serum, and urine with excellent repeatability and reproducibility. In contrast to uncoated filter paper, an improvement of 10-546-fold in sensitivity was achieved using PS-coated paper for paper spray, and an estimated lower limit of quantitation (LLOQs) in the range of 0.004-0.084 ng mL was obtained. The present study is significant in exploring the potential of PS for high-sensitivity MS analysis, and it provides a promising platform in the translation of the MS technique to clinical applications.

Determining Surface Energy of Porous Substrates by Spray Ionization

“…(2) Solvent for the peak ion current must have surface tension that allows intermediate wetting, less paper-solvent-analyte interaction and less analyte redeposition/redistribution post-extraction resulting in more efficient transfer to the mass spectrometer. 5 It will also have a moderate evaporation rate and large K value. (3) Solvent with high surface tension: low degree of wetting, low degree of paper-solvent-analyte interaction resulting in reduced extraction and low amount of re-deposition, low evaporation rate, and small K value.…”

A statistical approach to optimizing paper spray mass spectrometry parameters

“…As previously reported, the spray solvent composition affects both the recovery of the analyte and ion suppression. [25][26][27] To evaluate the spray solvent, a screening experiment using the middle pore size paper (Filter 5; 2.5 μm) and a medium solvent composition, 90:10 organic solvent:water with 0.1% FA, was performed for nine different solvents on four different paper coating types (hydrophobic, carbon-sputtered, untreated razor-cut Filter 5 paper, and laser-cut Whatman 31ET). The results showed an interaction between paper type and solvent type; the same solvent behaved differently depending on the paper coating type (Figure 2).…”

Fiber spray ionization mass spectrometry in forensic chemistry: A screening of drugs of abuse and direct determination of cocaine in urine

“…32 Therefore, the use of a low-polarity polymeric fiber has provided high sensitivity in the analysis of biological samples due to its hydrophobicity, morphology, and porosity. 32,34,35 The methodologies using polymeric fibers as substrates are currently known as fiber spray ionization mass spectrometry (FSI-MS) techniques, 36,37 which are based on an electrospray generation process from porous materials through capillary flow patented by Fenn, 38 as well as on nanoelectrospray production from a mesoporous polymer discussed by Tepper and Kessick. 39 Wang and co-workers showed the use of polystyrene (PS) microspheres in a hot-polymerization process to cover the surface of chromatographic paper, producing a PS-coated paper impregnated with microspheres used in the determination of therapeutic drugs, e.g.…”

“…The method showed excellent LOQ values of 4-84 pg/mL representing an improvement up to 546-fold in sensitivity compared with unmodified paper. 34 The modification of PS-coated paper using a baking process produced a glassy PScoated substrate with microspheres impregnated into the cellulosic fibers, which was applied in the analysis of proteins and peptides from whole blood. The results showed the glassy substrate presenting a sensitivity up to 1348 times better than paper in the detection of biomolecules from blood.…”