The three factors of the resolution (Rs)equation(see Equation 1.1)were explored in this thesis. During the course of the research project, an important aim was to explore separation processes that would lead to an increase in productivity without sacrificing Rs. To that end, an increase in the retention factor (k)to enhance Rs was deemed detrimental to the cycle time, hence the production rate, particularly when preparative separations are involved. Consequently the primary objectives were to (i)prepare more efficient columns and (ii)investigate new strategies in manipulating selectivity. The significance of the work contained in this thesis is highlighted in 27th International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2003)held in Nice, France between 15-19 June, 2003. Many of the papers presented significantly compared to chapters contained in this research / Doctor of Philosophy (PhD)

The advantages and disadvantages of packed capillary columns for high performance liquid chromatography are examined. Historically, the advantages are smaller sample and phase consumption, enhancement in sensitivity, easy column synthesis, higher obtainable efficiency, and easier interfacing to other techniques. These points are explored through experiments in microbore ion chromatography, packed fused silica columns, and capillary zone electrophoresis. These studies also address the disadvantages of microscale HPLC which are stringent instrument design, brittle or weak columns, poor column stability, and the lack of commercial instrumentation. The results of these investigations indicate the following. First, the purported sensitivity enhancement is really attributable to solute focusing and not to column miniaturization. Second, column synthesis is still a difficult procedure that requires experience. Third, higher efficiencies are realized, especially when the column diameter to particle diameter ratio is optimized. Fourth, interfacing to other techniques is simplified because of the lower volumetric flow rates. Finally, the only real disadvantages are stringent instrument design and brittle columns in some instances. This thesis offers means for circumventing these difficulties. / Ph. D.