Silica coated paper substrate for paper-spray analysis of therapeutic drugs in dried blood spots

Paper spray is a newly developed ambient ionization method that has been applied for direct qualitative and quantitative analysis of biological samples. The properties of the paper substrate and spray solution have a significant impact on the release of chemical compounds from complex sample matrices, the diffusion of the analytes through the substrate, and the formation of ions for mass spectrometry analysis. In this study, a commercially available silica-coated paper was explored in an attempt to improve the analysis of therapeutic drugs in dried blood spots (DBS). The dichloromethane/isopropanol solvent has been identified as an optimal spray solvent for the analysis. The comparison was made with paper spray using chromatography paper as substrate with methanol/water as solvent for the analysis of verapamil, citalopram, amitriptyline, lidocaine, and sunitinib in dried blood spots. It has been demonstrated that the efficiency of recovery of the analytes was notably improved with the silica coated paper and the limit of quantitation (LOQ) for the drug analysis was 0.1 ng mL ^-1 using a commercial triple quadrupole mass spectrometer. The use of silica paper substrate also resulted in a sensitivity improvement of 5-50-fold in comparison with chromatography papers, including the Whatman ET31 paper used for blood cards. Analysis using a hand-held miniature mass spectrometer Mini 11 gave LOQs of 10-20 ng mL ^-1 for the tested drugs, which is sufficient to cover the therapeutic ranges of these drugs.