Towards monitoring of the progress of chemical reactions using a novel plasma-assisted desorption ionisation mass spectrometry methodology

Abstract

A novel method for monitoring of pharmaceutically relevant reactions using PADI-MS has been developed in this study. The visible non-thermal plasma plume from a coaxial helium gas flow non-thermal RF plasma was optimised using a range of samples. PADI-MS was found to be a powerful analytical technique for pharmaceutically relevant solid and liquid samples and can readily be adapted for use in reaction monitoring. This study has determined that PADI-MS is fast, easy to set up and requires little or no sample preparation. PADI-MS has significant advantages over other techniques as it is faster, more sensitive and more convenient and suitable for investigation of complex molecules and mixtures. However, two limitations of PADI-MS are that the plasma can affect the sample surface chemistry upon exposure and quantification is not always trivial.

A number of other analytical methods were used in conjunction with PADI-MS: TLC, HPLC, FTIR and Raman spectroscopy. Chapter 3 investigated PADI-MS and Raman analysis of paracetamol tablet as model for pharmaceutically relevant solids. Raman microscopy was used to develop an understanding of how the plasma affects the sample surface. The plasma effect was also studied by examining changes in PADI-MS spectra.

In Chapter 4, PADI-MS acquisition settings were improved by adding water vapour to the outer He flow gas and increasing the plasma power to 8 W, optimising the analysis of mixture solutions from TLC plates. Although molecules could be identified with optimum sensitivity after separation, this may not be necessary, unless the highest possible sensitivity is required.

Chapter 5 deals with PADI-MS for direct analysis of pharmaceutical compounds in solid and liquid forms from glass slides and cotton swabs. PADI-MS was determined to besuitable for analysis of pharmaceutical tablets from solutions via both substrates, with distinct advantages for the latter.

The final Chapter studied PADI-MS for the monitoring of imine formation as model pharmaceutical reaction. Both FTIR and PADI-MS were successfully used, but the latter is faster and more versatile. TLC and HPLC could not be used for this reaction. PADI-MS was successfully used for this reaction using cotton swabs without preparation or pre-concentration of sample solutions.