Development and Application of Zirconia Coated Paper Substrate for High Sensitivity Analysis of Therapeutic Drugs in Dried Blood Spots

Abstract

Paper spray mass spectrometry has been demonstrated to be promising for direct analysis of therapeutic drugs in dried blood spots (DBS); however, the strong hydrogen bond and van de Waals interactions between paper substrate and analytes containing polar functional groups (e.g., therapeutic drugs) affect greatly the elution behavior and analysis sensitivity of compounds of interest during paper spray. Herein, we developed a one-sided ZrO2 coated paper substrate through a facile vacuum filtration approach using commercial ZrO2 particles as coating material and soluble starch as adhesive agent. Owing to the unique surface properties, as-prepared ZrO2 paper substrate has been shown to have excellent performance for analysis of therapeutic drugs in DBS during paper spray mass spectrometry. In contrast to original cellulose paper substrates, improvements of 43-189-fold in lower limit of quantitation (LLOQ) were obtained for the tested drugs using ZrO2 coated paper for paper spray. In comparing with the previously reported grade SG81 paper and one-sided silica coated paper, the LLOQs of the tested drugs with as-prepared ZrO2 paper decreased 1.5-16.5-fold relative to those from the above two, revealing that ZrO2 coated paper is a good candidate for paper spray in high sensitivity analysis of therapeutic drugs in DBS.

Ambient Ionization and Miniature Mass Spectrometry Systems for Disease Diagnosis and Therapeutic Monitoring

“…It is cross-validated against FDA (Food and Drug Administration) approved immunoassays and LC-MS/MS assays, showing comparable performance, but requiring much less sample preparation or expertise for sample handling 47 . In order to enhance the performance of PS, paper substrates coated with silica or metal oxide particles were also used for PS-MS analysis of drugs in blood samples; the sensitivity was found to be improved 5-189 times in comparison with use of chromatography paper substrates 48 , 49 .…”

Clinical Application of Ambient Ionization Mass Spectrometry

“…e effects of paper geometry, structure and materials have also been extensively investigated to improve the PSI-MS performance. 66,[68][69][70][71][72][73][74][75] It is relatively di cult for direct AIMS methods to obtain accurate quantitative analysis. is is usually carried out by spiking a known quantity of isotopically labeled standard.…”

Principles and applications of solid-substrate electrospray ionization mass spectrometry

“…Zhang等采用多种材料改变纸表面的性质, 包括二氧化 硅 [56] 、金属有机骨架(MOFs)材料 [57] 、氧化镁 [58] 、铜基 催化剂 [59] 、氧化锆 [60] 、硅树脂 [61] 、金属粉末等 [61] . 其 他课题组也在纸喷雾的改性方面取得了重要进展.…”