Preview	PDF (Whole thesis) whole_CampbellK...pdf | Download (14MB) Available under University of Tasmania Standard License. | Preview
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Abstract

Existing comprehensive drug screening procedures employ either batteries of
analytical techniques which target specific drugs and structurally related drug groups,
or relatively non-specific broad screens for either acidic or basic drugs which require
additional confirmation of the identity of drugs detected. A single, automated, semiquantitative
gas chromatography/mass spectrometry (GC/MS) screening procedure
for approximately 100 structurally and chemically diverse drugs in 2.5 mL of whole
blood was developed and validated. A drug extraction strategy was developed which
employed both liquid-liquid and solid-phase extraction techniques to produce four
blood extracts for separate GC/MS analysis in selected ion monitoring (SIM) mode.
The chromatograms produced were processed automatically by a novel macro which
generated reports detailing the drugs identified and their approximate concentrations
in blood.
Target drugs were selected for potential inclusion in the screening procedure on the
basis of their ability to impair driving performance, their toxicological significance
(forensic application) and their relative prevalence in the community (clinical
application). As licit and illicit drug use in the community changes, these target
drugs would change, however, those selected were representative of a range of
chemical structures and functionalities broad enough to permit the development of a
general analytical screening procedure which could be applicable to additional drugs.
The qualitative and quantitative characteristics of underivatised and derivatised
(butyl- and pentafluoropropionyl-) target drugs were investigated to:-
1. determine retention indices and select suitable target m/z ions by which drugs
would be identified;
2. establish quantitative parameters which were then used to estimate blood drug
concentrations;
3. determine instrument detection limits and establish whether or not they were
comparable with expected therapeutic drug blood concentrations; and
4. identify drugs not suitable for GC/MS analysis.
The recovery of 90% of target drugs was greater than 75% using the automated drug
screening procedure.
The automated drug screening procedure was validated in blood specimens from a
forensic laboratory and a hospital. The procedure identified 97% of drugs spiked at
known concentrations in blood specimens prepared as part of a Proficiency Testing
Program for Australian and New Zealand forensic laboratories. The developed
screening procedure compared favourably with current toxicological methods
routinely employed at the Government Analytical and Forensic Laboratory
(Tasmania), identifying a greater number of drugs in the same blood specimens.
During the analysis of blood specimens from hospital patients, it was found that the
screening procedure was likely to identify the majority of drugs at therapeutic levels
particularly if the blood taken was from an individual who had been previously
administered the drug within two half-lives. A pilot study which identified the drugs present in the blood of a limited sample of
Tasmanian drivers involved in road traffic accidents indicated the applicability of the
drug screen to studies which investigate the possible causal role of drugs in road
accidents. The suitability of the screening procedure to other clinical and forensic
applications was indicated.

Item Type:	Thesis - PhD
Authors/Creators:	Campbell, Kathryn
Copyright Holders:	The Author
Copyright Information:	Copyright 1997 the Author - The University is continuing to endeavour to trace the copyright owner(s) and in the meantime this item has been reproduced here in good faith. We would be pleased to hear from the copyright owner(s).
Additional Information:	Thesis (Ph.D.)--University of Tasmania, 1997. Includes bibliographical references. Contents: Comprehensive broad drug screen in whole blood -- Chromatography of drugs -- Alkylation and chromatography of alkyl derivatives -- Acylation and chromatography of pentafluoropropionyl derivatives -- Development of a drug screening strategy for whole blood -- Validation of the automated semi-quantitative broad drug screening procedure
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