Ambient ionization mass spectrometry for the forensic screening of pharmaceuticals and the determination of potential drug candidates.

摘要

The ability of generating ions directly from solid samples, in their native state without the need for sample preparation is rapidly changing the field of mass spectrometry (MS). The key technological innovations enabling these advancements include the development of atmospheric pressure ionization MS interfaces and the introduction of ambient ionization technologies. Pioneered by desorption electrospray ionization (DESI) introduced by Cooks and coworkers in 2004, and followed closely by direct analysis in real time (DART) introduced by Cody et al. in 2005, ambient MS methods allow removal of sample size and shape constrains, thereby making many objects amenable to direct MS analysis. The elimination of sample preparation requirements allows rapid analysis times, making such mass spectrometric methodologies more amicable over other techniques where throughput is sought, especially when dealing with the analysis of a large sample set.;The work presented in this thesis is aimed at studying some of the fundamental processes prevailing in ambient mass spectrometry, and the application of these techniques to the detection of molecules of pharmaceutical importance. A review of the state-of-the art in ambient mass spectrometry is presented in Chapter 1. Chapter 2 presents the first implementation of DESI MS to the chemical fingerprinting of counterfeit drug tablets that mimic the vital anti-malarial artesunate. Chapter 3 presents an investigation of the effect of performing various ion-molecule reactions in the charged liquid droplet/solid sample boundary in DESI and its effect on the selectivity, gas phase stability and the associated analyte ion yields for the determination of artesunate in drug tablets. Chapter 4 presents the direct quantitation of artesunate in solid antimalarial tablets by DESI MS. Chapter 5 presents the development of a selective and sensitive DESI MS protocol for screening of TamifluRTM quality. Chapter 6 presents an implementation of DESI MS in imaging mode. In Chapter 7, an investigation of the complementarity between DESI and DART is presented, enabling the development of a robust multimode ambient ion source.