"Advances in and Applications of Capillary Scale Liquid Chromatography" by Samuel William Foster

Date Approved

6-2-2025

Embargo Period

6-2-2025

Document Type

Dissertation

Degree Name

Ph.D. Pharmaceutical Chemistry

Department

Chemistry and Biochemistry

College

College of Science & Mathematics

Advisor

James Grinias, Ph.D.

Committee Member 1

Subash Jonnalagadda, Ph.D.

Committee Member 2

Milton Lee, Ph.D.

Committee Member 3

Amos Mugweru, Ph.D.

Committee Member 4

Lei Yu, Ph.D.

Keywords

Capillary Scale Liquid Chromatography;HPLC;Liquid Chromatography

Disciplines

Analytical Chemistry | Chemistry | Physical Sciences and Mathematics

Abstract

Analytical-scale high performance liquid chromatography (HPLC) is one of the most widely used analytical techniques in the world. Efforts have been made to reduce the mobile phase consumption of HPLC by reducing the inner diameter (I.D.) of the column. By using capillary-scale columns (< 0.5 mm I.D.), separations can be performed with orders of magnitude less solvent consumption. This work describes advances made to capillary scale instrumentation as well as applications enabled by these advances. A compact capillary-scale LC was used for the analysis of numerous pharmaceutical and illicit drug compounds for point of need analysis. A miniaturized mass spectrometer was coupled to this instrument for on-line reaction monitoring within a standard chemical fume hood. Kinetic profiles of commercially available capillary columns were developed in order to provide guidance to others during column selection. The implementation of a column oven improved the analysis of large biopharmaceuticals. Several critical quality attributes of monoclonal antibodies including fragmentation, charge variants, and glycosylation profiles were able to be determined on the capillary scale. These results will help to make capillary-scale liquid chromatography a more viable solution for chromatographic analysis.

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