Liquid chromatography coupled with tandem mass spectrometry for the quantitative analysis of anticancer drugs in biological matrices

Abstract

In this thesis, the development and validation of liquid chromatography tandem mass spectrometric (LC-MS/MS) methods for the quantitative bioanalysis of anticancer drugs are described. The monitoring of these drugs in biological fluids and tissues is important during both pre-clinical and clinical development and often in routine clinical use. Traditionally, liquid chromatography (LC) in combination with ultraviolet (UV), fluorescence, or electrochemical detection is employed for this purpose. The successful hyphenation of LC and mass spectrometry (MS), however, has dramatically changed this. MS detection provides better sensitivity and selectivity than UV detection and, in addition, is applicable to a significantly larger group of compounds than fluorescence or electrochemical detection. From the analytical methods described in this thesis, it can be concluded that LC-MS/MS is very suitable for sensitive and selective quantitation of anticancer agents in biological samples. Furthermore, LC with an alkaline mobile phase in combination with MS detection in the positive ion mode appeared very useful for the analysis of four agents described in this thesis. This system may be applicable to other basic drugs. Finally, the use of internal standards is discussed. Stable isotopically labeled internal standards are the first choice, but deuterium labeled compounds may demonstrate unexpected behavior.

In summary, in this thesis the development and validation of LC-MS/MS methods for several anticancer agents are described. These assays were developed in order to support clinical pharmacological studies. LC-MS/MS appeared to be very suitable for this purpose. Hopefully, this thesis has made a contribution to medicinal cancer therapy.