Item – Theses Canada

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OCLC number
455769350
Link(s) to full text
LAC copy
LAC copy
Author
Jessome, Lori Lee,1982-
Title
Insight into the ionizationdesorption and ion suppression in MALDI of small drug molecules.
Degree
M. Sc. -- Dalhousie University, 2006
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2007]
Description
2 microfiches
Notes
Includes bibliographical references.
Abstract
The aim of this study was to gain some insight into the ionization/desorption and ion suppression mechanism of matrix-assisted laser desorption/ionization (MALDI) of small molecules. The small molecules used throughout the study were a series of cinchona alkaloids, many of which were from the quinine/quinidine class of pharmaceutical drugs. By way of this study the fragmentation pathways of the compounds were investigated and mechanisms were proposed. It was noted that all the quinine/quinidine compounds share a common fragmentation pathway. As well, the thermodynamic properties, gas phase basicity (GB) and proton affinity (PA), were determined for the compounds for the first time to the author's knowledge, using the well established Kinetic method and a novel MALDI method. The good agreement between the values obtained between the two methods (<4 kJ/mol), indicate that the assumption that the MALDI method was based, namely that at least a pseudo-thermodynamic equilibrium is achieved in the MALDI plume, is true. Calibration plots obtained for the alkaloids reveal that MALDI/QqQ provides a useful means of small compound analysis, with low limit of detection (<0.1 [mu]M) and broad dynamic ranges (e.g., 0.16-100 [mu]M). Monitoring ion suppression in plasma it was seen that even with sample preparation (protein precipitation) on average all of the compounds experienced 30% suppression. By investigating the phenomenon further it was seen that analyte suppression occurs at low suppressor concentration even before complete matrix suppression. As well, it was seen that the extent of suppression an analyte experiences is related inversely to its GB or PA, meaning the lower GB a compound the more suppressed it is. However, it was noted that the relative concentration of an analyte out weighs its GB in determining the success of its ionization. Comparing the extent suppression of the structurally similar analytes it was observed that they experienced quite a broad range of suppression, up to 50%. Observing the ion suppression of preformed ions it was concluded that the charge of an analyte affects the degree of its suppression, related to counter ions that require separation. It is expected by the results obtained in the studies that protons obtained from either matrix or analyte enable the neutralization and thus separation of the counter ion. Conversely, ion suppression studies seem to indicate that neutral analytes require excited matrix molecules to facilitate their ionization.
ISBN
9780494269183
0494269189