Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.797172
Title: The diagnostic use of alternate samples in forensic toxicology
Author: Wylie, Fiona Mary
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2001
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Abstract:
The use of biological specimens other than blood and urine for the detection of drugs, usually referred to as alternative specimens, has been the focus of many scientific studies over the past two decades. The type of biological sample analysed affects the type of information obtained and the aims of this project were to investigate hair, saliva and nail as alternative specimens and to evaluate their diagnostic use in Forensic Toxicology. The potential of hair analysis as a diagnostic tool in Forensic Toxicology was investigated by developing and validating a robust and reliable method for the simultaneous determination of opiates and methadone in hair samples. An assessment was made of the ability of three different pretreatment steps involving enzymatic hydrolysis, acid hydrolysis and solvent washing to extract morphine, codeine, 6-monoacetylmorphine, methadone and EDDP from hair. The methanol procedure was the only one that did not hydrolyse a percentage of 6-monoacetylmorphine to morphine and this was used for subsequent analyses, followed by solid phase extraction (SPE) and gas chromatography-mass spectrometry (GC/MS). Post-mortem hair samples from suspected heroin overdose cases were analysed using the validated method to determine whether each individual was a heroin user and their history of heroin exposure. An overall indication of drug use was produced for each individual from the results of analyses of hair and post-mortem blood. Known drug use history was established from police reports and the hair analysis results were evaluated against the available information. The ranges of concentrations of analytes found in hair were; morphine 0.10 - 9.79 ng/mg, codeine 0.12 - 3.47 ng/mg, 6-monoacetylmorphine 0.14 - 70.07 ng/mg, methadone 0.15 - 1.15 ng/mg and EDDP 0.27 - 1.55 ng/mg. A total of 31 hair samples was analysed, the majority of which were shown to be from regular heroin users. Criteria were established from the data which allowed users to be categorised into low, medium and high regular users with respect to their heroin habit. Periods of compliance with methadone programmes or drug rehabilitation programmes were also evident. The data supported the conclusion that hair analysis can successfully determine the drug use history of heroin users. The number of cases involving fluoxetine and paroxetine has increased in the last 5 years and has required the development of improved methods to quantitate these drugs in whole blood. In addition, blood analysis provides the reference data for evaluation of analytical results from alternative specimens. An SPE method using cyanopropyl columns was developed and evaluated initially for the extraction of fluoxetine and its metabolite, norfluoxetine. This method was compared with existing liquid-liquid extraction methods and validated using both high performance liquid chromatography (HPLC) and GC/MS. The HPLC method was found to work well with clinical blood samples but was subject to problems caused by co-extracted interferences from some post-mortem blood samples. By contrast, the GC/MS method did not exhibit this problem and was selected for further analyses. The method was validated for the simultaneous analysis of fluoxetine, norfluoxetine and paroxetine and was shown to achieve significantly improved limits of detection for each of these analytes of approximately 1 ng/ml. Post-mortem and clinical blood samples from antidepressant users were successfully analysed using this improved method, these results provided the foundation for further research into the diagnostic use of alternative biological specimens and were compared with data from hair, saliva and urine from the same cases. The method developed for antidepressants in blood was also found to extract these analytes efficiently from saliva. One conclusion from this study was that saliva can be used as an alternative specimen to blood or urine to indicate recent drug exposure. The analysis of hair as a means of determining chronic administration of prescription drugs was assessed by developing a procedure for the analysis of fluoxetine, norfluoxetine and paroxetine in hair samples obtained from geriatric and clinical patients. Methanol wash and acidic hydrolysis pre-treatments were assessed for these drugs. The latter produced higher recoveries without deterioration of the analytes and was used for analysis of hair samples from antidepressant users, to give a history of their drug administration, and these results were assessed against information obtained from each patient's medical records.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.797172  DOI: Not available
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