title: Silica coated paper substrate for paper-spray analysis of therapeutic drugs in dried blood spots.
abstract: 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.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United States.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Manicke
authors.forename: R Graham
authors.initials: RG
authors.lastname: Cooks
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ouyang
mesh_terms: D001800:Blood Specimen Collection / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D010209:Paper; D004364:Pharmaceutical Preparations / Q000032:analysis*; D012680:Sensitivity and Specificity; D012822:Silicon Dioxide / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D014700:Verapamil / Q000032:analysis
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents; D012822:Silicon Dioxide; D014700:Verapamil