Development of quantitative bioanalytical methods for the measurement of pharmaceutical compounds via HPLC-UV and HPLC-MS/MS.

摘要

Research in pharmaceutical treatments for illnesses and disease processes has rapidly grown in the past decade. The field is fueled by advances in our understanding of the molecular mechanics of the human body, coupled with the development of sophisticated scientific instruments which can efficiently generate massive amounts of important data. This has led to an ever-growing need for the development of quantitative bioanalytical methods to measure pharmaceutical compounds.;In this work, the theory behind the analytical processes and instruments that make these investigations possible is discussed. Further, the development of two high performance liquid chromatographic (HPLC) methods with both ultra violet (UV) spectrometry and mass spectrometry (MS) detection of the cannabinoid (CB) antagonists' rimonabant and surinabant is presented. The methods developed for the CB antagonists' are successfully applied to animal studies in clinical and pre-clinical investigations. Thirdly, preliminary work is included which was conducted for the development of two methods to be used in the measurement of anti-cancer agents, quinacrine and triapine. Finally, a discussion is presented for the consideration of the challenges and potential solutions in the development of an HPLC-MS method for triapine.;The theory, experimental designs and results discussed here demonstrates how analytical chemistry and instrumentation are used in bioanalytical method development. This research also illustrates how once developed, these methods serve to advance the progress in biochemical, preclinical and clinical studies.