Direct analysis of dried blood spots by mass spectrometry.

摘要

Dried blood spots (DBS) have become a popular method for sample collection in recent years. Blood is a popular biofluid for many different types of analyses, particularly pharmacokinetic and toxicokinetic studies. For these studies, dried blood spot sampling has often taken the place of liquid blood collection. This is partially due to the biohazardous nature of blood, as well as the difficulties and costs in shipping liquid blood.;Most DBS studies use liquid chromatography--tandem mass spectrometry (LC-MSn) for analysis. In these analyses, the dried blood spots must be extracted from their paper substrate. While LC offers separation of blood background compounds from analytes of interest, there are disadvantages to this method, including manual punching of cards, lack of automation and dilution of sample.;The research presented in this dissertation explores direct analysis methods of DBS that do not require extraction. The first project of this research uses matrix-assisted laser desorption ionization (MALDI) tandem mass spectrometry to analyze dried blood spot samples. In these experiments, the only sample preparation needed is coating the DBS samples with matrix prior to analysis. A method for quantification of exogenous compounds in blood via MALDI-MS n was optimized using the technique of wide-isolation. Wide-isolation MALDI-MSn allows for the analyte and internal standard signal to be analyzed in a single isolation window. The second project uses paper spray ionization tandem mass spectrometry (PS-MSn) to analyze and develop quantification of compounds in blood. Paper spray is an ambient ionization technique that allows for direct analysis of a paper substrate. DBS analysis via PS-MSn does not require extraction of the sample prior to analysis, as in LC-MS, nor does it require the sample to be coated in matrix, as with MALDI-MS.;Finally, the third project of this research explores solvent optimization of paper spray ionization mass spectrometry to potentially separate a metabolite from its parent compound. This research attempts to exploit the polarity compatibility between solvents and analytes to perform on-line separation of paper spray ionization samples.