Advances in the application of high performance affinity chromatography to bioanalysis and approaches for improving the quality and reliability of bioanalytical data.

摘要

This dissertation covers a range of topics important to the advancement of the field of bioanalytical chemistry. Three of the chapters are principally focused on the study and use of affinity ligands in bioanalytical and clinical chemistry. The other two chapters address topics related to quality issues in the practice of bioanalysis. These chapters are diverse in content and also in the approach to their study for this dissertation.;The first section of the dissertation consists of the first three chapters. In this section the content of the first chapter was developed through extensive laboratory work culminating in the development of a prototype system for the use of mass spectrometry as a detection mechanism in affinity chromatography applied to the measurement of the free fraction of a drug. The second chapter of this section describes the development of computer simulations to model reversible binding in affinity chromatography to help design, predict, and confirm the performance of various applications in affinity chromatography. The final chapter of this section provides an overview on the many applications of the use of affinity ligands in mass spectrometry.;The second section of the dissertation consists of two chapters that cover critical components of quality analytical method development and data generation in bioanalysis. The first chapter in this section presents a new approach that was developed for LC/MS/MS system suitability determination in the application of bioanalysis. The second chapter of this section is devoted to educating the bioanalytical industry with a thorough review and discussion of issues with stability of drugs and metabolites in biological matrices.