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

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.