Previously, we showed how to make and use stable zirconia RPLC media, introducing two new techniques, thermally tuned tandem column (T3C) chromatography and high temperature ultra-fast liquid chromatography (HTUFLC). We now propose to make and characterize a number of innovative highly stable silica (SiO2) phases that will use hypercrosslinked surface polymer networks confined to a monolayer on the silica surface. We will then apply these materials to the high-speed analysis of pharmaceuticals, environmental and workplace toxicants, and ultimately, in collaboration with Professor David Muddiman, to complex biological samples. Our goal is to explore all aspects of the new derivatization technology, including conventional LC, packed capillary LC and capillary electrochromatography. We will explore two general concepts in HPLC made possible by the availability of high stability phases. First, we propose to develop fast, comprehensive two-dimensional HPLC (2D-LC) based on our phases. Due to the thermal limitations of conventional supports, the advantages of using high temperatures in HPLC have hardly been explored. In particular, upon increasing the temperature to 200 degrees C, the resulting 20-fold decrease in viscosity gives a nearly 20-fold increase in analysis speed. We will use the high speed of HTUFLC to increase the speed of 2D-LC and make it a much more practical routine method. The use of higher temperatures also facilitates the use of longer columns, especially in a capillary format, particularly for microdetection. Second, we propose to extend the isocratic T3C concept to gradient elution chromatography. Both approaches are predicated on the availability of phases of high thermal stability.