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Dissertation
Applications of Tandem Column Liquid Chromatography for the Achiral and Chiral Separation of Selected Classes of Pharmaceuticals
Doctor of Philosophy (Ph.D.), Drexel University
Sep 2024
DOI:
https://doi.org/10.17918/00010715
Abstract
Tandem column-liquid chromatography (TC-LC) is a type of high performance liquid chromatography (HPLC) that is designed to improve selectivity, resolution, and efficiency by coupling two columns together in series. TC-LC was used in both chiral and achiral separations of pharmaceutical compounds. A liquid chromatographic method was developed to separate ten non-steroidal anti-inflammatory drugs (NSAIDs) (aceclofenac, aspirin, carprofen, celecoxib, diclofenac, flurbiprofen, ibuprofen, ketoprofen, naproxen, salicylic acid) using an achiral tandem column configuration under reversed-phase conditions. An NSAID test mix was prepared with 0.5 mg/mL thiourea as a t0 marker and 0.5 mg/mL of each of the above NSAIDs in 1:1 acetonitrile: aqueous 0.2% formic acid. Three different 5-cm columns were investigated individually and in two different tandem-column configurations: an octyl (C8), a perfluorophenyl (PFP) column, and a biphenyl (BP) column. The two tandem configurations were a PFP column followed by either a BP or C8 column. While baseline resolution of the critical pair of NSAIDs (ketoprofen + naproxen) was not achieved with the PFP+C8 combination, the PFP+BP combination gave baseline resolution of all 10 NSAIDs in under 25 minutes. A tandem-column liquid chromatographic method was developed to separate five beta-blockers (Acebutolol, Alprenolol, Atenolol, Metoprolol, Propranolol) from each other and additionally their enantiomers. A beta-blocker test mix was prepared with 0.75 mg/mL of each of the above beta-blockers in 25: 75 methanol: water. This method employed a column with an achiral stationary phase (HALO-PCS-C18) coupled to a column with a chiral stationary phase (NicoShell). The chemical name of the latter is a proprietary modified macrocyclic glycopeptide. Using a shallow gradient increasing from 40% of a polar ionic mobile phase of 0.1 weight percent ammonium formate in methanol to 60% with the other mobile phase component of aqueous 0.1 % ammonium formate, five beta-blockers and their enantiomers were separated in under 10 minutes. Although baseline resolution of the Alprenolol enantiomers was not achieved, this method achieved the complete achiral and chiral separation of the other four beta-blockers and their enantiomers.
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Details
- Title
- Applications of Tandem Column Liquid Chromatography for the Achiral and Chiral Separation of Selected Classes of Pharmaceuticals
- Creators
- Megan Elizabeth Marrazzo
- Contributors
- Daniel B. King (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xix, 107 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Arts and Sciences; Chemistry; Drexel University
- Other Identifier
- 991021906710004721