Development, characterization, and application of paper spray ionization.

Paper spray is developed as a direct sampling ionization method for mass spectrometric analysis of complex mixtures. Ions of analyte are generated by applying a high voltage to a paper triangle wetted with a small volume (<10 microL) of solution. Samples can be preloaded onto the paper, added with the wetting solution, or transferred from surfaces using the paper as a wipe. It is demonstrated that paper spray is applicable to the analysis of a wide variety of compounds, including small organic compounds, peptides, and proteins. Procedures are developed for analysis of dried biofluid spots and applied to therapeutic drug monitoring with whole blood samples and to illicit drug detection in raw urine samples. Limits of detection of 50 ng/mL (or 20 pg absolute) are achieved for atenolol in bovine blood. The combination of sample collection from surfaces and paper spray ionization also enables fast chemical screening at high sensitivity, for example 100 pg of heroin distributed on a surface and agrochemicals on fruit peels are detectable. Online derivatization with a preloaded reagent is demonstrated for analysis of cholesterol in human serum. The combination of paper spray with miniature mass spectrometers offers a powerful impetus to wide application of mass spectrometry in nonlaboratory environments.