Studies of cyclic nucleotides and pharmaceutical products by mass spectrometry

• Main Author: Bayliss, M. A.
• Published: Swansea University 1997
• Subjects: 543
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.636061

Electrospray ionisation, atmospheric pressure chemical ionisation and fast atom bombardment ionisation have been discussed in this thesis and applied to the analysis of a number of potentially important pharmaceutical compounds, some in the form of complex mixtures. Combinatorial chemistry, a synthetic method for the mass production of potential drug candidates, has emerged in the last five years finding wide acceptance in the pharmaceutical industry. Using one such library, containing some one hundred compounds, a method was developed with allowed for the screening of the sample using high performance liquid chromatography coupled with mass spectrometry. A key objective of the project was the minimisation of sample usage during the analytical phase. It has also been demonstrated that it is possible to use mass spectrometry as an analytical tool in the simultaneous detection of more than one analyte important for determining reaction kinetics in biological assays. Key to any process of quantitation has to be an element of structural confirmation which has been carried out on a selection of novel compounds which are to form the basis of a large number of future biological assays. An in-depth study of a compound used in radiography is detailed allowing identification of related products, during initial product manufacture, and scale-up to full manufacturing capacity. Potential degradation compounds have been investigated following stress testing of the drug designed to predict compounds formed during the storage life of the product. Esoteric mobile phases for liquid chromatography sometimes need to be employed in order to achieve selectivity. In many cases these methods involve the use of involatile buffer systems which are not directly compatible with mass spectrometry. Using a system of collecting the separated peaks, trapping and elution, it was demonstrated that it is possible to remove these troublesome buffers and obtain high quality mass spectrometric data.