Chemical Profiling of Drugs and Metabolites from Complex Biological Matrices by Atmospheric Pressure and Ambient Ionization Mass Spectrometry

Atmospheric pressure and ambient mass spectrometry (MS) techniques are powerful analytical tools for the omics technologies. Ambient MS techniques allow for the surface analysis of molecules directly from substrates and thin biological tissue sections with minimal to no sample pretreatment in the open environment. This dissertation describes the development and implementation of rapid and novel MS based methods for the analysis of targeted analytes such as drugs and metabolites from complex biological matrices in two main fields of application, drug development and phytometabolomics. We explored the potential of quantitative mass spectrometry imaging (MSI) by the ambient MS technique, desorption electrospray ionization-mass spectrometry (DESI-MS). The discovery of quantitation MSI methods were explored and evaluated based on its analytical figures of merit (precision, accuracy, linearity, and so forth). Triple threat methods covering the identification, quantification and mapping the spatial distribution of analytes from biological tissue sections opens new avenues in MSI. The development of targeted qualitative and quantitative ESI-MS, DESI-MS and multistage mass spectrometry, DESI-MSn, methods for plant metabolomics were also investigated. DESI-MS and DESI-MSn methods coupled offline to normal phase high performance thin layer chromatography (HPTLC) and C18 functionalized reverse phase (RPTLC) were created to identify and separate bioactive secondary metabolites from natural products such as seeds, roots, twigs, and leaves. The implementation of these rapid, robust and high-throughput methods allowed for the discovery of novel phytochemicals in the plant species under investigation.