Current applications of high-resolution mass spectrometry in drug metabolism studies.

This paper reviews high-resolution mass spectrometry (HRMS) approaches published in 2007-2011 for the elucidation of drug metabolism with a focus on new therapeutics, new drugs of abuse, and doping agents using time-of-flight, single-stage Orbitrap, ion trap Orbitrap, and other Fourier transform MS-based techniques. The present review provides an overview of metabolite-generating systems and assays used, sample preparation techniques, ionization and fragmentation techniques, as well as data mining strategies and software tools which were used in the reviewed papers. Furthermore, HRMS-specific topics such as demand for a certain resolution or a specific mass accuracy are discussed in detail and corresponding recommendations are given. Finally, the advantages and limitations of these methods are discussed.