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 co-elute under non-alkaline, ambient temperature conditions.

Figure 1: Fast separation of structurally-diverse, basic solutes at 80 °C.

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.

Analytes

1. Ephedrine

2. Norephedrine

3. Nicotine

4. Metoprolol

5. Quinine

6. Doxylamine

7. Diphenhydramine

8. Nortriptyline

9. Amitriptyline

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