Multidimensional ion mobility (IM) and mass spectrometry separations have been applied successfully to the analysis of a wide range of analytes and demonstrate potential as a selective and high throughput analytical technique.
The direct analysis of pharmaceutical formulations from non-bonded reversed-phase thin layer chromatography (RP-TLC) plates by desorption electrospray ionisation (DESI) combined with drift tube ion mobility-mass spectrometry (IM-MS) has been investigated. The detection of active pharmaceutical ingredients is demonstrated with, and without, chromatographic separation of the active ingredients and formulation excipients. Varying the solvent composition of the DESI spray using a gradient allows selective desorption of pharmaceutical ingredients from the surface of the RP-TLC plate.
The potential of IM-MS in combination with high performance liquid chromatography (LC) for the metabonomic analysis of rat urine is reported. The approach allowed the acquisition of nested data sets, with mass spectra acquired at regular intervals during each IM separation and several IM spectra acquired during the elution of an LC peak. The application of LC combined with field asymmetric waveform ion mobility spectrometry (FAIMS) and ion trap mass spectrometry to a metabonomic study of rat urine, with subsequent data mining by artificial neural networks, allowed discrimination between young and old rats on the basis of LC-FAIMS-MS profiles.
The application of IM-MS to real-time reaction monitoring has also been investigated. Real-time reaction monitoring was carried out over a period of several hours, with the reaction mixture sampled and analysed at intervals of several minutes. Results indicate that spectral quality is improved when employing IM-MS, compared to mass spectrometry alone, as the complexity of the reaction mixture increases with time. The combined IM-MS approach has potential as a rapid and selective technique to aid pharmaceutical process control and for the elucidation of reaction mechanism.
A Doctoral Thesis. Submitted in partial fulfillment of the requirements for the award of Doctor of Philosophy of Loughborough University.