The novel 1.5 mm ID stainless steel Fused-Core columns push the performance of UHPLC-MS systems by delivering more sensitivity and 50% less solvent consumption than 2.1 mm ID columns. With their hardware design, the columns offer ease of implementation to the front-end LC allowing for their use on commercial analytical flow UHPLC-MS instrumentation. The benefits of moving from 2.1 mm to the new, robust 1.5 mm ID columns will be demonstrated using low molecular weight pharmaceuticals. In addition, a biopharmaceutical case study will be presented using LC-MS analysis of intact and reduced trastuzumab. Furthermore, to further reap the sensitivity benefits of the 1.5 mm column, the proper tubing and fittings will be discussed for miniaturization of the LC-MS system.