The power of ce : illustrations of the unrivaled selectivity of capillary electrophoresis ; quantitative analysis of polypeptides from rat plasma by liquid chromatography/mass spectrometry
Delinsky, David Christian
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This dissertation is divided into two parts. Part I. The Power of CE: Illustrations of the Unrivaled Selectivity of Capillary Electrophoresis and Part II. Quantitative Analysis of Polypeptides from Rat Plasma by Liquid Chromatography/Mass Spectrometry. The purpose is to describe state of the art technologies in bio-analytical chemistry and how they can be applied for pharmaceutical and biomedical analysis. The introduction highlights the history of separation sciences and describes modern biological sample preparation, separation methodology, and detection using mass spectrometry. Part I, as the title suggests, focuses on capillary electrophoresis and how this extraordinarily selective separation technique can be used to resolve, not only compounds with very similar structure, but individual chiral enantiomers of drugs as well. Chapter 1 describes a method for the quantitative determination of several barbiturates from meconium. The method could be used to assess fetal exposure to barbiturate drugs. Chapter 2 demonstrates a method that is able to selectively monitor two enantiomeric forms of an antiviral drug for the study of possible preferential metabolism of one enantiomer over the other. Part II presents several related methods for the quantitation of polypeptides of various sizes from blood plasma. In general, peptide quantitative analysis has been difficult without the use of immunoassays. In chapters 3-5, we demonstrate how HPLC/MS methods can be used to quantify polypeptides from plasma in support of pharmacokinetic studies. This could be a useful tool for the biotechnology industry as peptide based drugs are developed and ultimately brought to the marketplace.