Using Superficially Porous Particles and Ultrahigh Pressure Liquid Chromatography in Pharmacopeial Monograph Modernization of Common Analgesics

The higher pressures and flow rates needed to increase throughput in ultrahigh pressure liquid chromatography (UHPLC) can lead to thermal broadening due to viscous friction. The use of superficially porous particles and still air thermal environments can help reduce this broadening, but this has not yet been studied for applied, isocratic methods. Here, the use of five columns with varying lengths, diameters, and particle sizes were investigated for increased analytical throughput of pharmacopeial monograph methods for two over-the-counter analgesic drugs. System suitability parameters (resolution and peak asymmetry) and temperature changes across the axial length of the column were monitored at conditions near column or system pressure limits. Results from these investigations indicated that a 2.1x50-mm column packed with 2.6 mu m particles provides the best opportunity for increased throughput, which was demonstrated with a 20-s cycle time method for the separation of four compounds (two active pharmaceutical ingredients, one impurity, and one internal standard) while maintaining a baseline resolution of 1.5 between all peaks.