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Title: Development of electrochemical methods for the determination of pharmaceutical impurities
Author: Channon, Robert B.
ISNI:       0000 0004 5915 2156
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2015
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This thesis is concerned with the development of electrochemical approaches for the determination of carcinogenic genotoxic impurities in pharmaceuticals. Investigations focus on the genotoxic impurity hydrazine as it is a particularly challenging species for current methodologies used in the pharmaceutical industry. A metal nanoparticle functionalised polycrystalline boron-doped diamond macroelectrode is utilised for hydrazine determination in stationary solution, in the presence of two important electrochemically active, inner sphere, active pharmaceutical ingredients, namely acetaminophen and promazine. It is shown that this sensor can be tuned for the application by simply changing the chemical identity of the nanoparticles. A new design of flow cell for flow injection analysis is then developed, in order to exploit a hydrodynamic approach for the electrochemical determination of genotoxic impurities. The bespoke flow cell is combined with an inlaid boron doped diamond microband electrode and the flow injection analysis response is analysed numerically and against various models of dispersion to demonstrate the quality of the method. Finally, this flow injection analysis sensor is employed for the trace detection of hydrazine in a large excess of acetaminophen. Quantitation is demonstrated down to 0.274 parts per millions with respect to the amount of acetaminophen - surpassing the required safe guidelines set by the pharmaceutical industry for the quantitation of genotoxic impurities.
Supervisor: Not available Sponsor: Engineering and Physical Sciences Research Council ; AstraZeneca
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RM Therapeutics. Pharmacology