Impurities in active pharmaceutical ingredients (APIs) include volatile and involatile organic compounds and inorganic anions and cations. The impurities in an API are acquired during the manufacturing process and may arise from impurities in reagents, side reactions and may, as in the case of ionic impurities associate with the molecule during purification processes. Impurity levels have to be controlled to conform to pharmacopoeial requirements; although this is less apparent in the case of organic and inorganic counterions. In the work reported in this thesis four applications of impurity profiling in APIs and API intermediates were investigated. In chapter 3 the removal of impurities in lipoic acid prior to crystallisation was investigated using high resolution mass spectrometry in combination with chemometric modelling of the data. Several impurities of lipoic acid were characterised by using MSn and the success of the purification process in removing impurities was verified. In chapter 4 the organic impurities in chlorpheniramine maleate were investigated using high resolution mass spectrometry in combination with chemometric modelling of the data. Several new impurities of chlorpheniramine maleate were characterised by using MSn and it was demonstrated that it was possible to distinguish between different manufacturers’ batches of chlorpheniramine maleate according to their impurity profiles by using high resolution mass spectrometry data in combination with chemometric modelling.In chapter 5 the anionic impurities in different pharmaceutical bases were investigated by using capillary ion chromatography. The different pharmaceutical bases contained a wide range of trace ions as well as the main counter-anion. Aside from the anions being present as impurities they might have an impact of processing procedures such as crystallisation. In chapter 6 a range of techniques including nuclear magnetic resonance spectroscopy, high resolution LC-MSn, headspace gas chromatography mass spectrometry, anion and cation chromatography were applied to the analysis of 6-aminopenicillanic acid (6-APA) samples, provided by GSK, which had of low to high clarity values. It was not possible to find any direct association between clarity readings and the various impurity profiles although a number of new impurities in 6-APA were characterised.
|Date of Award||28 Sep 2017|
- University Of Strathclyde
|Supervisor||David Watson (Supervisor) & Blair Johnston (Supervisor)|