The Diagnostic Use of Alternate Samples in Forensic Toxicology Thesis submitted in Accordance with the Requirements of the University o f Glasgow for the Degree of Doctor of Philosophy by Fiona Mary Wylie BSc (HONS), A.M.R.S.C. Department of Forensic Medicine and Science November 2001 Copyright © Fiona M. Wylie 2001 ProQuest Number: 13833985 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 13833985 Published by ProQuest LLC(2019). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 fGLASGOW UNIVERSITY .LIBRARY: , IXSRG CD PM \ Acknowledgements I would like to thank Dr. John S. Oliver for his support and guidance as supervisor and for giving me encouragement to complete this. Thanks also to the Department of Forensic Medicine and Science, University of Glasgow for financial support. I would also like to take this opportunity to express my gratitude to the pathologists of the Department of Forensic Medicine and Science, University of Glasgow, Prof. D. Stott, Glasgow Royal Infirmary, Dr. McQueen, Drug Problem Service, Glasgow and medical staff at Lightbum Hospital and Bridgeton Health Centre for the collection of biological specimens and to all of those who kindly donated samples to make this work possible. Thanks to all members of staff and students in the Department of Forensic Medicine and Science for help, advice, entertaining tea-breaks and nights-out. A special thanks to Alison Seymour who has listened to many a problem and who always makes me look on the bright side when all seems at a loss and to Gail Cooper for her enthusiasm which never fails to encourage me. Finally, thanks to Kirsty and Colin for managing to live with me for so long, the rest of my friends for keeping me entertained, my brother, Ewan, for not finishing before me and my mum and dad for so many things I would not know where to start - thanks for everything. Contents i List of Figures................................................................................................................ix List of Tables................................................................................................................xii Summary........................................................................................................................xv List of Abbreviations.............................................................................................. xviii 1 INTRODUCTION.................................................................................................... 1 2 H AIR...........................................................................................................................3 2.1 Introduction ..........................................................................................................................................3 2 .2 S t r u c t u r e o f t h e H a ir s h a f t ....................................................................................................3 2.2.1 Cuticle.............................................................................................................4 2.2.2 Cortex..............................................................................................................4 2.2.3 Medulla........................................................................................................... 4 2.2.4 Pigment Granules..........................................................................................5 2 .3 T h e HAIR FOLLICLE............................................................................................................................... 5 2 .4 H a ir g r o w t h c y c l e ......................................................................................................................... 6 2.4.1 A nagen phase................................................................................................ 6 2.4.2 Catagen phase............................................................................................... 6 2.4.3 Telogen phase.................................................................................................6 2 .5 H a ir g r o w t h r a t e ...........................................................................................................................6 2 .6 D r u g incorporation in t o h a i r ............................................................................................. 7 2 .7 D r u g p r o p e r t ie s a f f e c t in g incorporation in t o h a i r ........................................8 2.7.1 Lipophilicity................................................................................................... 8 2.7.2 Basicity...........................................................................................................8 2.7.3 Melanin Affinity.............................................................................................9 2.7.4 Structural Factors........................................................................................ 9 2.7.5 Other factors affecting drug incorporation .............................into hair 10 2 .8 C o l l e c t io n o f h a i r ..................................................................................................................... 10 2.8.1 Methods....................................................................................................... 10 2.8.2 Sample size..................................................................................................10 2.8.3 Hair type...................................................................................................... 11 2 .9 S t a b il it y o f d r u g s in h a i r .................................................................................................... 11 2 .1 0 E t n h i c b i a s .........................................................................................................................................11 2.1 1 C ontamination ............................................................................................................................. 12 2 .1 2 A n a l y s i s .............................................................................................................................................13 2.12.1 Decontamination........................................................................................13 Contents ii 2.12.2 Removal of drug from hair matrix...........................................................13 2.12.3 Extraction...................................................................................................14 2.12.4 Analysis......................................................................................................14 2 .1 3 Interpretation o f a m o u n t s o f d r u g d e t e c t e d in h a i r ......................................14 2.13.1 Dose-concentration correlations............................................................. 14 2.13.2 Cut-off levels...............................................................................................15 3 HAIR ANALYSIS FOR OPIATES AND METHADONE............................16 3.1 A i m ................................................................................................................................................................16 3 .2 Introduction ........................................................................................................................................16 3.2.1 Opiates.........................................................................................................16 3.2.2 Methadone..................................................................................................17 3.3 C h e m i s t r y ...............................................................................................................................................17 3.3.1 Opiates........................................................................................................ 17 3.3.2 Methadone..................................................................................................18 3 .4 M e t a b o l is m a n d e x c r e t io n ......................................................................................................18 3.4.1 Opiates........................................................................................................ 18 3.4.2 Methadone..................................................................................................19 3.5 P harmacokinetics ..........................................................................................................................2 0 3.5.1 Opiates........................................................................................................ 20 3.5.2 Methadone................................................................................................. 21 3 .6 T o x i c i t y..................................................................................................................................................21 3.6.1 Opiates.......................................................................................................