| The matrix plays an essential role in matrix-assisted laser desorption/ionization (MALDI). The major goal of the research described in this thesis is to develop a new matrix system with improved sample homogeneity and signal reproducibility that could be a substitute for the widely used solid matrices. Room temperature ionic liquids have high solubilizing power, negligible vapor pressure, and broad liquid range. They form homogeneous solutions with most analytes and promote their ionization. Ionic liquid matrices (ILMs) produce much improved signal reproducibility, which minimizes the time required to search for "sweet spots" that permit acquisition of high quality mass spectra, and facilitates the quantitative studies in MALDI. In this thesis, we report the advantages and limitations of ILMs with respect to solid matrices.; We utilized ILMs in the quantitative analysis of a single oligonucleotide, polypeptide, and small protein, taking advantage of their much-improved sample homogeneity. Good calibrations with high linearity and reproducibility can be achieved over a dynamic range of two orders of magnitude even when the internal standard has a structure different from those of the analytes. We further quantified the peptides in simple and complex mixtures. The good linearity and reproducibility for the calibration curves were retained; however, the dynamic range for quantification was reduced to one order of magnitude for complex mixture analysis.; We then applied ILMs for analysis of phospholipids. Higher signal intensity, smaller spot size, improved spot homogeneity, better signal reproducibility and comparable or better detection limits, and a lower extent of prompt fragmentation were achieved with ILMs compared to the crystalline matrix 2,5-dihydroxybenzoic acid (2,5-DHB).; We also sought improvement in a specific analysis problem by developing a derivatization approach to improve quantification of diacyl glycerols (DAGs) using electrospray ionization mass spectrometry (ESI/MS). A quaternary ammonium cation was introduced to neutral DAG molecules by using N-chlorobetainyl chloride. The permanent charge introduced in the derivatized DAGs allowed us to achieve two orders of magnitude higher signal intensities than with their underivatized sodium adducts. We demonstrated that this reverse derivatization is suitable for the quantification of DAG molecular species in biological samples when using ESI/MS. |
