Date Approved

8-6-2020

Embargo Period

8-6-2022

Document Type

Thesis

Degree Name

M.S. Pharmaceutical Sciences

Department

Chemistry and Biochemistry

College

College of Science & Mathematics

Advisor

Grinias, James P.

Committee Member 1

Mugweru, Amos

Committee Member 2

Jonnalaggadda, Subash

Keywords

high-throughput, method development, monograph, pharmaceuticals, superficially porous particles, ultrahigh pressure liquid chromatography

Subject(s)

Drug development; Liquid chromatography

Disciplines

Medicinal Chemistry and Pharmaceutics

Abstract

The higher pressures and flow rates needed to increase throughput in ultra-high 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, which is especially important in applications requiring high-throughput, isocratic separations, such as monograph methods for over-the-counter analgesics. In the first experiment discussed below, 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 this investigation indicated that shorter columns packed with 2.6 µm particles provide the best opportunity for increased throughput, which was demonstrated with a 20 s cycle time method for the separation of four compounds while maintaining a baseline resolution of 1.5 between all peaks. This was the basis for the idea of creating a method qualification protocol of an adapted ibuprofen method. Linearity, accuracy, recovery and repeatability measurements were completed in 16 minutes using this approach, a sequence that often requires a full day of analysis. These results demonstrate the capability of modern instrumentation to readily implement high-throughput LC methods into qualified pharmaceutical workflows.

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