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Title: The role of liquid chromatography-high resolution mass spectrometry in the diagnosis and treatment of substance misuse
Author: Murch, Sarah Louise
ISNI:       0000 0004 7223 5685
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2018
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Substance misuse remains problematic with current concerns being the rise in acute poisoning deaths, particularly opioid-associated, and the ever-widening range of drugs available. Strategies for tackling opioid addiction and opioid related-deaths include researching alternative routes of therapeutic agent administration. Initial urine screening for substance misuse has traditionally employed immunoassays, with confirmation of specific analytes by chromatographic methods. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) offers untargeted analysis without compromising selectivity, and enables users to ascertain putative elemental compositions of an analyte, retrospectively interrogate data, and to incorporate novel analytes easily. These features enable screening and confirmation of drugs in a single method, and may be advantageous for detecting novel psychoactive substances (NPS). This thesis aims to investigate the role of LC-HRMS in drug analysis in the clinical setting. A simple system was developed that is capable of detecting a wide range of commonly-encountered drugs and metabolites. Non-selective sample preparation was used to enable detection of as many compounds as possible, but significant matrix effects were observed. Additional information regarding selected NPS was ascertained through retrospective identification of mephedrone metabolites in patient urines, and through later incorporation of ethylphenidate, methylphenidate, and ritalinic acid, into the method. A separate quantitative LC-HRMS method was developed to facilitate pharmacokinetic studies of naloxone and naltrexone administered through alternative routes. The method was also applied to urine samples, with naloxone-3-glucuronide identified as a potential marker to differentiate between Subutex and Suboxone use. LC-HRMS has advantages in drug detection, particularly in regard to NPS, and in method development. However, application in the clinical setting is restricted by requirements for high throughput, timely results, and operation to accepted ‘cutoff’ values that introduce awkward compromises in system operation. LC-HRMS may have greater application in the forensic setting where more time is available for the analysis of a single sample.
Supervisor: Taylor, David Michael Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available