The use of recently developed mass spectrometry approaches for the characterisation of biological mixtures

Abstract

The thesis describes a number of examples of the use of recently developed mass spectrometry experimental approaches to characterise biologically important mixtures. The recently introduced field of ambient ionisation mass spectrometry has been utilised in the rapid, sensitive, information rich characterisation of pharmaceutical formulations. Little, or no, sample treatment was required and the experiments were shown to provide detailed information on active ingredients in the presence of a number of other components. A number of ambient ionisation approaches including DART, DESI and DAPCI were compared and advantages and disadvantages of each approach outlined and discussed. The exciting technology of ion mobility has recently been commercially interfaced with mass spectrometry (IMMS). This has been utilised in a series of fundamental experiments that probe the interaction of varied cations with isomeric oligomers of carbohydrates. The approach enables conformational changes to be rapidly measured over a wide (500-6000 Da) mass range. Changes in conformations were observed for multiply cationised species which agree with previously measured solution phase measurements. The IMMS approach has also been used successfully to characterise a number of Nlinked glycans released from glycoproteins. The experiments enable isomeric structures to be differentiated and present an opportunity to develop a rapid, high information content screen. Estimated cross sectional measurements have been calculated and found to be in good agreement with those obtained from conventional drift cell approaches