posted on 2023-05-27, 07:37authored byCampbell, Kathryn
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.
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). 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