The detection of pharmaceutical drug compounds from intact biological tissue by matrix-assisted laser desorption/ionization (MALDI) quadrupole ion trap mass spectrometry

The aim of the work presented in this dissertation was to investigate the use of matrix-assisted laser desorption ionization (MALDI) for detecting pharmaceutical drug compounds from intact biological tissues. This research was also designed to evaluate the potential of laser desorption ionization on a quadrupole ion trap for future laser microprobe applications. Research efforts on this project were focused in three major areas: fundamental studies, instrumentation, and applications.;In the first stage of the project, experiments were performed to evaluate and optimize the MALDI process for drugs in a model tissue matrix (matrigel) using a commercial MALDI-time-of-flight instrument. Two central nervous system drug compounds, spiperone and ephedrine, were studied using the MALDI matrix 2,5-dihydroxybenzoic acid. Results of these initial experiments showed that the concentration of the matrix solution, the polarity of the matrix solvent, and the crystallization speed of the matrix were all important in increasing the production of analyte ion signal from the model tissue.;In the second stage of the project, a novel laser desorption quadrupole ion trap instrument was constructed for analyzing drug compounds from more complex tissues. The instrument was constructed using a Finnigan series 4500 electron ionization/chemical ionization source, a DC quadrupole deflector, and a Finnigan ITS40 quadrupole ion trap mass analyzer. The advantage of this instrument over current laser microprobe instruments is that it is capable of performing multiple stages of mass spectrometry (MS;In the final stage of the project, the new instrument was used to analyze several pharmaceutical drug compounds from tissue samples obtained directly from test species. MALDI spectra were obtained for the antipsychotic drug compound spiperone from incubated rat cerebral tissue. Experiments were also performed on samples of human plasma spiked with the peptide antibiotic polymyxin B...