Date of Award

12-12-2022

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Dr. David Wilson

Second Advisor

Dr. Jun Yin

Third Advisor

Dr. Gabor Patonay

Abstract

Capillary electrochromatography (CEC) is one of the capillary electrophoresis (CE) modes that have been hyphenated to mass spectrometry (MS of MS/MS) for the analysis of both neutral and charged analytes with shorter analysis time, higher column efficiency, higher sensitivity, good selectivity, and much lower sample consumption. This research expands CEC-MS applications in the kynurenine pathway of tryptophan catabolism, builds insights into the molecular recognition mechanism in hydrophilic interaction CEC (HICEC), and develops a monolithic CEC-based exploratory quantitative approach. Chapter 1 presents an overview of a number of several essential aspects related to capillary electrochromatography (CEC) and CEC hyphenated to mass spectrometry (CEC-MS or CEC-MS/MS). A literature survey was performed within the databases Wiley Online Library, ScienceDirect, PMC/PubMed, Web of Sciences, and other sources by google search. A total of 163 studies reporting qualitative and quantitative analysis of achiral CEC and CEC-MS or CEC-MS/MS were identified and reviewed. Chapter 2 delineated the open tubular CEC-MS method development, optimization, and validation for the qualitative and quantitative analyses of kynurenine pathway metabolites in the human plasma sample. Validation parameters such as limit of detection (LOD), limit of quantitation (LOQ), linearity range, recovery, precision, and accuracy were established according to FDA guidelines. The endogenous concentration of the metabolites and pairs of the level of metabolites with significant positive correlation for inflammatory biomarkers [C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α)] were statistically evaluated. Chapter 3 described the development and comparison between the retention models based on linear solvation energy relationships (LSER) and its modified version hydrophilic subtraction model (HSM). The calculation of the retention factor was modified for CEC, which showed a good fit in the HSM model. Chapter 4 aimed at developing a scoring approach to compare the performance of different CEC-MS monolithic stationary phases (SPs). The proposed score reflects the potential of a set of CEC-MS conditions to provide useful analytical information for a given compound and the best signal selected from the different detected adducts. The scores allowed the evaluation of each stationary phase and optimized the number of CEC monoliths needed to analyze test solutes.

DOI

https://doi.org/10.57709/32646904

File Upload Confirmation

1

Share

COinS