Liquid Chromatography - Triple Quadrupole Mass Spectrometry : The gold standard for quantitative bioanalysis of anti-cancer agents

Abstract

To understand the pharmacologic mechanisms of action, efficacy and toxicity of any anti-cancer drug it is important to know how the compound is transformed in the body: either into active metabolites or inactive and toxic (degradation) products. This information may lead to the success or failure of a drug in arresting cancer cell growth, and facilitates the design of more effective drugs. To quantify the drug and to follow its absorption, distribution, metabolism, and elimination (ADME) in body fluids, ultra sensitive and specific analytical methods are of pivotal importance. In recent years, High Performance Liquid Chromatography coupled to tandem Mass Spectrometry (HPLC-MS/MS) technique has shown a steep, fascinating development into the most powerful and important tool in the quantitative determination of investigational anti-cancer agents and identification of metabolites. For this thesis, the major aim was to develop and to validate sensitive analytical HPLC-MS/MS methods for the analysis of anticancer agents, metabolites and degradation products in biological matrices. These methods were applied to support pharmacokinetic studies of established and experimental anticancer agents. For our studies we selected the investigational cytotoxic agents: apaziquone (EO9), 5-methylindirubine and the licensed drugs: paclitaxel, gemcitabine and capecitabine.