Novel approaches to the analysis of benzodiazepines and morphine-related analytes in forensic samples

Webb, R

Novel approaches to the analysis of benzodiazepines and morphine-related analytes in forensic samples

Webb, R

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Publication Type:: Thesis
Issue Date:: 2005

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Field	Value	Language
dc.contributor.author	Webb, R
dc.date.accessioned	2015-10-13T01:57:52Z
dc.date.available	2015-10-13T01:57:52Z
dc.date.issued	2005
dc.identifier.uri	http://hdl.handle.net/10453/37474
dc.description	University of Technology, Sydney. Dept. of Chemistry, Materials and Forensic Science.	en_US
dc.description.abstract	This research has focused on the development of analytical methods for the quantification of benzodiazepines and opiates in forensic samples. Both these classes of drugs are regularly encountered in forensic toxicology, especially in cases of fatal heroin overdose, and thus quantitative methods for their analysis are particularly relevant. Chapter 1 outlines the nature of the heroin problem in Australia and the different drug policies currently employed to help reduce the problems associated with heroin use and overdose. The involvement of metabolic factors and CNS depressants, such as benzodiazepines, in heroin overdose is discussed. An introduction to post-mortem drug analysis, as well as a comprehensive review of previously published methods for the analysis of heroin, its metabolites and benzodiazepines in biological samples, is presented. Chapter 2 describes procedures for the synthesis of commonly encountered morphine and benzodiazepine metabolites as an alternative to purchasing these metabolites commercially. Yields of 48, 25, 74 and 70% were obtained for M3G, M6G, 7-aminonitrazepam and 7-aminoclonazepam respectively. Chapter 3 documents the development of a rapid capillary zone electrophoresis (CZE) method for the analysis of nine benzodiazepines using dynamically prepared doubly-coated capillaries, consisting of a polycation of poly(diallyldimethylammonium chloride) (PDDAC) and a polyanion of dextran sulfate (DS). The addition of cyclodextrins to the background electrolyte (BGE) was also investigated as a means of improving analysis time. The validated method was successfully applied to the analysis of spiked beverages, with run times of less than 6.5 minutes. Chapter 4 describes the optimisation of a gradient HPLC separation of nine benzodiazepines using artificial neural networks (ANNs) in conjunction with experimental design. Various outputs and types of training data were investigated to yield the most appropriate ANN, which gave predictive errors of less than 5% for six of the nine analytes studied. A novel chromatographic function was also developed as a means of assessing the quality of chromatographic separations. The optimised method was validated for blood and successfully applied to authentic post-mortem samples. The limits of detection of the method ranged from 0.0057 to 0.023 pg/mL, and recoveries were in the order of 58 - 92%. Chapter 5 details the development of a simple and rapid HPLC method for the simultaneous determination of morphine, M3G, M6G and codeine. Following SPE, the analytes were determined in post-mortem blood samples taken from heroin- related deaths. Cases involving the use of benzodiazepines in conjunction with heroin were found to have lower ratios of M6G/MOR and M3G/MOR, suggesting rapid death following heroin administration. M6G/M3G ratios were calculated to investigate the possible contribution of M6G towards heroin overdose with respect to its potential analgesic activity. M6G/M3G ratios were higher in cases involving the use of heroin only.	en_US
dc.format	Thesis (PhD)	en_US
dc.language.iso	en	en_US
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/37474/10/02whole.pdf
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	au.edu.uts.lib/ppc
dc.subject	Forensic toxicology.	en
dc.subject	Benzodiazepines and opiates.	en
dc.subject	Capillary zone electrophoresis (CZE) method.	en
dc.subject	Contribution of M6G.	en
dc.subject	Heroin overdose.	en
dc.title	Novel approaches to the analysis of benzodiazepines and morphine-related analytes in forensic samples	en_US
dc.type	Thesis
utslib.copyright.status	open_access

Abstract:

This research has focused on the development of analytical methods for the quantification of benzodiazepines and opiates in forensic samples. Both these classes of drugs are regularly encountered in forensic toxicology, especially in cases of fatal heroin overdose, and thus quantitative methods for their analysis are particularly relevant. Chapter 1 outlines the nature of the heroin problem in Australia and the different drug policies currently employed to help reduce the problems associated with heroin use and overdose. The involvement of metabolic factors and CNS depressants, such as benzodiazepines, in heroin overdose is discussed. An introduction to post-mortem drug analysis, as well as a comprehensive review of previously published methods for the analysis of heroin, its metabolites and benzodiazepines in biological samples, is presented. Chapter 2 describes procedures for the synthesis of commonly encountered morphine and benzodiazepine metabolites as an alternative to purchasing these metabolites commercially. Yields of 48, 25, 74 and 70% were obtained for M3G, M6G, 7-aminonitrazepam and 7-aminoclonazepam respectively. Chapter 3 documents the development of a rapid capillary zone electrophoresis (CZE) method for the analysis of nine benzodiazepines using dynamically prepared doubly-coated capillaries, consisting of a polycation of poly(diallyldimethylammonium chloride) (PDDAC) and a polyanion of dextran sulfate (DS). The addition of cyclodextrins to the background electrolyte (BGE) was also investigated as a means of improving analysis time. The validated method was successfully applied to the analysis of spiked beverages, with run times of less than 6.5 minutes. Chapter 4 describes the optimisation of a gradient HPLC separation of nine benzodiazepines using artificial neural networks (ANNs) in conjunction with experimental design. Various outputs and types of training data were investigated to yield the most appropriate ANN, which gave predictive errors of less than 5% for six of the nine analytes studied. A novel chromatographic function was also developed as a means of assessing the quality of chromatographic separations. The optimised method was validated for blood and successfully applied to authentic post-mortem samples. The limits of detection of the method ranged from 0.0057 to 0.023 pg/mL, and recoveries were in the order of 58 - 92%. Chapter 5 details the development of a simple and rapid HPLC method for the simultaneous determination of morphine, M3G, M6G and codeine. Following SPE, the analytes were determined in post-mortem blood samples taken from heroin- related deaths. Cases involving the use of benzodiazepines in conjunction with heroin were found to have lower ratios of M6G/MOR and M3G/MOR, suggesting rapid death following heroin administration. M6G/M3G ratios were calculated to investigate the possible contribution of M6G towards heroin overdose with respect to its potential analgesic activity. M6G/M3G ratios were higher in cases involving the use of heroin only.

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