Hassan, Huda (2011) An evaluation of the stability and prevalence of alcohol and related biomarkers in biological matrices with applications to the interpretation of medico-legal cases. PhD thesis. http://theses.gla.ac.uk/3002/ Copyright and moral rights for this thesis are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the Author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the Author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Glasgow Theses Service http://theses.gla.ac.uk/ [email protected] An Evaluation of the Stability and Prevalence of Alcohol and Related Biomarkers in Biological Matrices with Application to the Interpretation of Medico-Legal Cases Thesis Submitted in Accordance with the Requirements of the University of Glasgow for the Degree of Doctor of Philosophy by HUDA MUSTAFA A. HASSAN Forensic Medicine and Science (School of Medicine) November 2011 © Huda Mustafa A.Hassan To my parents Mustafa and Ameera " وَُ رب ارََُْْ آََ رََِ ًَِا" "And say: My Lord! Bestow on them Your Mercy as they did bring me up when I was small" iii Acknowledgement First I would like to thank God for all of my blessings, His infinite liberality will always exceed all our wishes and our thoughts. I would like to thank King Abdullah (Custodian of the Two Holy Mosques) for his kindness and generosity, the Saudi Government, Royal Embassy, Saudi Cultural Bureau and Ministry of Higher Education, as well as King Faisal Specialist Hospital and Research Center in Riyadh (Pathology laboratory, Academic Affairs and Hospital Administration) for my scholarship and supporting my study not only financially. I would like to express my sincere gratitude to my supervisor Dr. Gail Cooper for her enthusiasm, her inspiration, and her great efforts that helped guide me throughout my research and the writing of my thesis. With her support she helped make this thesis possible. She always did so many thoughtful things that had her special touch, I have no other words other than, thank you, thank you, thank you! I must also thank all of the Toxicologists, Dr. Robert Anderson for all his support and lots of good ideas and tips to support my research, Dr. Hazel Torrance for her encouragement, advice and support, and great tips especially during the LC-MS/MS project. My sincere thanks also go to Dr. Karen Scott for all her advice and support. She was the one who enlightened me at the start of my research by helping me to operate and set up methods on the GC/MS. I would also like to take this opportunity to thank Dr. Fiona Wylie, and Dr. Eleanor Miller and to wish them all the best. Many thanks to Dr. John Clark for his kindness, I really liked when he would wish me a good morning or see you tomorrow in Arabic. I would like to express my thanks to the Technicians who helped me get to grips with some of the equipment and for all their support during my research, and to all of the staff within Forensic Medicine and Science; the Secretaries, Administrators and IT staff for all their support. I must say that Forensic Medicine and Science was like a second home for me and made me feel so welcome. It is an excellent place to come and study with fantastic resources and great staff who encourage you. I would also like to thank and recognize the University of Glasgow Staff especially in the School of Medicine, the Graduate School, the International Office, Library, IT help desk, courses tutors, and all other staff because with their support I have had a great environment to study and continue my research without obstacle. I feel very happy and honored to have had the opportunity of studying at such a distinguished institution and with such a distinguished team. iv Warm thanks to Professor Maceij Bogusz who encouraged and supported me to apply for my PhD and for inviting me work as a co-author of a chapter in his book. For also supporting me during my work with him at the King Faisal Hospital and throughout my PhD, without which I could not have achieved so much! To my late Dad, whose memories inspired me to persevere. I will not forget to thank my lovely mother who always prays for God to help me and to make my life easier. I also value the support of my eldest brother Abdulkader, all brothers and sisters in Saudia Arabia who always kept in touch with me and made me feel surrounded by a loving family. I would also like to express my deepest gratitude to my late husband, Sameer (SAM - his favorite name) who always advised and encourage me before he passed away during my first year of my PhD to continue my study no matter what happened. Also I cannot forget my four children, Mashael, Sarah, Mishaal and Ali who have been ever so patient when I had to leave them for long periods of time during the busy parts of my research and for helping me at home. I knew they were very proud of me, especially when I have won awards or had success during my studies. They give me strength in my life and have supported me during the difficult times. Thank you! I would like to extend my thanks to all friends and colleagues specially Dr. Abdulkareem Alfazil who is the one whose understanding and virtue I can equally confide and whose opinion I can value for its wisdom and its sincerity. I will not forget to extend my thanks to our family’s friend Mr. Naveed for his great support since we arrived to Glasgow and during difficult time. Many thanks for my neighbours Elina and family for their kindness and care. Finally, this thesis could not have been possible without all the support I have had and I hope my work will benefit my country and other countries in some way. Huda Hassan October 2011 v Table of Contents ACKNOWLEDGEMENT ......................................................................................................................... III LIST OF TABLES .................................................................................................................................. IX LIST OF FIGURES ................................................................................................................................ XI LIST OF APPENDICES ........................................................................................................................ XIII AUTHOR'S DECLARATION ................................................................................................................ XIV ABSTRACT .................................................................................................... XV LIST OF ABBREVIATIONS ................................................................................................................ XVII CHAPTER 1 - INTRODUCTION .............................................................................................................. 1 1.1 History of Alcohol Use .................................................................................................................... 1 1.1.1 Alcohol Standard Measure .......................................................................... 2 1.2 Prevalence of Alcohol Use ............................................................................................................ 3 1.3 Alcohol-Related Harm .................................................................................................................... 4 1.3.1 Alcohol-Rehlated Social Harm ..................................................................... 5 1.3.2 Alcohol-Related Deaths ............................................................................. 6 1.3.3 Road Traffic Incidents Involving Alcohol ......................................................... 8 1.3.4 Foetal Alcohol Spectrum Disorders (FASD) ...................................................... 9 1.3.5 Alcohol-Related Harm Reduction Plan in Scotland ............................................ 13 1.4 Interpretative Challenges Associated with Medico-legal Investigations Involving Ethanol ............................................................................................................................................. 14 1.5 Pharmacokinetics of Ethanol ...................................................................................................... 14 1.6 Other Volatiles of Interest .......................................................................................................... 17 1.7 Sample Selection for the Analysis of Volatiles ....................................................................... 18 1.8 Stability of Alcohol in Post-Mortem Blood ............................................................................... 22 1.9 Analysis of Ethanol and Related Volatiles ............................................................................... 23 1.9.1 Headspace Gas Chromatography-Flame Ionization Detection (HS-GC-FID) ............... 24 1.9.2 Selection of a Suitable Internal Standard for Analysis of Volatiles ........................ 25 1.9.3 Analytical Considerations for Method Development (Volatiles) ............................ 28 1.10 Analytical Biomarkers of Alcohol Consumption ..................................................................... 29 1.10.1 Introduction .....................................................................................