MALDI-MS of drugs: Profiling, imaging, and steps towards quantitative analysis

Matrix-assisted laser desorption/ionization (MALDI) is a soft ionization technique which can be used in mass spectrometry to produce ions from biomolecules without inducing the fragmentation associated with traditional methods of ionization. When used with small molecules, the lack of fragmentation allows identification of specific molecules against a background of alternative signals; thus, for example, the presence of drug molecules and metabolites can be distinguished from a range of alternative biomolecules present within a tissue sample. Using highly collimated lasers in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) allows imaging of a tissue sample whereby the laser is rastered across the sample and individual mass spectra are collected in a serial manner. Thus, the distribution of the molecules within the tissue sample can be presented in the form of a 2D image. While the detection of specific drug molecules and metabolites within biological samples has its uses, quantification of those same molecules would be of greater benefit in a clinical setting. However, accurate quantification presents additional challenges. We present an overview of the MALDI-MS technique followed by recent progress in profiling drugs and their metabolites through imaging drug distributions within tissues and finish with recent developments in the quantification of drugs in tissues by MALDI-MSI.