High pH and Elevated Temperatures for Fast Separation of Strongly Basic Drug Compounds

Two important but frequently underutilized tools in methods development are mobile-phase pH and elevated temperatures. Hamilton's PRP-C18 column is well-suited for high pH and high temperature applications because the polymer-based stationary phase is chemically inert and has excellent thermal stability above 100 °C.

In modern drug discovery, where analytical HPLC can be a bottleneck, production is streamlined through the use of shorter columns with smaller particles, operated at higher flow rates. The flexibility to employ a high pH mobile phase and elevated temperatures represents further valuable tactics in methods development. These tools, often underutilized or not practical with silica-based columns, enable rapid separation of closely-related basic solutes in their charge-neutral forms that would otherwise be coeluted under non-alkaline, ambient temperature conditions.

In this study, nine structurally-diverse, strongly basic drug compounds are resolved in less than 2 min using a high pH mobile phase and a fast acetonitrile gradient at 80 °C.

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