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Download Thesisadobe Non-targeted analysis of new psychoactive substances using mass spectrometric techniques by Daniel J. Pasin, MRACI A thesis submitted for the Degree of Doctor of Philosophy (Science) University of Technology Sydney 2018 Certificate of authorship and originality I certify that the work in this thesis has not previously been submitted for a degree nor has it been submitted as part of the requirements for a degree except as fully acknowledged within the text. I also certify that the thesis has been written by me. Any help that I have received in my research work and the preparation of the thesis itself has been acknowledged. In addition, I certify that all the information sources and literature used are indicated in the thesis. This research is supported by an Australian Government Research Training Program Scholarship. Production Note: Signature removed prior to publication. Daniel J. Pasin, MRACI 26/02/2018 Acknowledgements Acknowledgements Firstly, I would like to extend my deepest thanks to my primary supervisor, Associate Professor Shanlin Fu. You have been my primary supervisor for both my honours and PhD degrees and over these last 5 years, you have been nothing but supportive, patient and encouraging. I could always rely on you to provide timely feedback and you were always happy to endorse me for post-PhD opportunities. It has been a great pleasure to complete my PhD research under your supervision. I would also like to thank my co-supervisors, Dr. Adam Cawley and Dr. Sergei Bidny. Without your external collaboration, the success of this project could not be possible. Furthermore, I wish to acknowledge the staff at the Australian Racing Forensic Laboratory (ARFL) and Forensic Toxicology Laboratory at NSW FASS for your assistance in this project. Furthermore, I would like to thank them for the financial support throughout this project including the purchase of reference materials and providing an external scholarship top-up. Thank you to all the UTS academic and professional staff for your assistance throughout my project even though I was not in the laboratory much - I know Ron Shimmon will miss me dearly. I would also like to thank the Centre of Forensic Science and Professor Claude Roux for allowing me so many opportunities to present my research at domestic and international conferences. This has subsequently provided me invaluable contacts that will be no doubt be beneficial in the future. To the UTS friends that I have made over the last couple of years, thank you for making my time during my PhD and living in Sydney enjoyable - I always know that I have somewhere to stay if I am in Europe. I would also like to thank Morgan “Mo” Philp for being a great colleague putting up with me at conferences and my general nonsense. - i - Acknowledgements Lastly, I want to express my deepest gratitude to my family for supporting me throughout my PhD journey both emotionally and financially. You have always encouraged me to do my best and it has allowed me to achieve something that I never thought possible and love you all dearly. - ii - Table of contents Table of contents Acknowledgements ...................................................................................................... i List of figures .............................................................................................................. x List of tables ............................................................................................................. xiv List of abbreviations ................................................................................................ xv Publications and conference proceedings ............................................................ xxii Abstract .................................................................................................................. xxvi CHAPTER 1: INTRODUCTION ......................................................................... 1 1.1 A brief overview of new psychoactive substances ............................................... 2 1.1.1 Synthetic cathinones .................................................................................. 3 1.1.2 Hallucinogenic phenethylamines .............................................................. 4 1.1.3 Synthetic cannabinoids .............................................................................. 6 1.1.4 Other NPS derivatives ............................................................................... 8 1.1.4.1 Psychedelic tryptamines .............................................................. 8 1.1.4.2 Piperazines .................................................................................. 9 1.1.4.3 Synthetic opioids ....................................................................... 10 1.1.5 References ............................................................................................... 11 1.2 PUBLICATION: Current applications of high-resolution mass spectrometry for the analysis of new psychoactive substances: a critical review (doi: 10.1007/s00216-017-0441-4) .............................................................................. 15 1.2.1 Foreword ................................................................................................. 15 1.2.2 Abstract ................................................................................................... 17 1.2.3 Keywords ................................................................................................ 17 1.2.4 Introduction ............................................................................................. 18 1.2.5 Analysis of NPS using HRMS ................................................................ 19 - iii - Table of contents 1.2.6 Overview of the role HRMS in different analytical contexts.................. 20 1.2.7 Sample preparation .................................................................................. 23 1.2.7.1 Seized materials and purchased legal highs .............................. 23 1.2.7.2 Biological matrices ................................................................... 23 1.2.8 Instrumental analysis techniques ............................................................. 25 1.2.8.1 Conventional separation techniques coupled to HRMS ........... 25 1.2.8.2 Direct sample analysis techniques coupled to HRMS .............. 26 1.2.9 Data acquisition ....................................................................................... 30 1.2.9.1 Data-dependent MS/MS acquisition ......................................... 30 1.2.9.2 Data-independent MS/MS acquisition ...................................... 33 1.2.9.3 MSn acquisition ......................................................................... 34 1.2.10 Data processing techniques ..................................................................... 34 1.2.10.1Targeted screening .................................................................... 35 1.2.10.2Suspect screening ...................................................................... 36 1.2.11 Non-targeted/untargeted screening strategies ......................................... 38 1.2.11.1Top-down non-targeted screening ............................................ 40 1.2.11.2Bottom-up non-targeted screening ............................................ 44 1.2.11.3Component identification .......................................................... 46 1.2.12 Conclusions and perspectives ................................................................. 47 1.2.13 References ............................................................................................... 48 1.3 Aims of the project .............................................................................................. 55 CHAPTER 2: TOP-DOWN SCREENING STRATEGIES .............................. 56 2.1 Rationale ............................................................................................................. 57 2.2 Mass defect filtering (MDF) ............................................................................... 58 2.2.1 Introduction ............................................................................................. 58 - iv - Table of contents 2.2.2 Methods and materials ............................................................................ 61 2.2.2.1 Mass defect ranges of NPS ....................................................... 61 2.2.2.2 Chemicals and reagents ............................................................. 61 2.2.2.3 Specimen collection .................................................................. 61 2.2.2.4 Preparation of stock solutions ................................................... 62 2.2.2.5 Preparation of working solutions .............................................. 62 2.2.2.6 Preparation of fortified biological samples ............................... 62 2.2.2.7 Instrumental analysis ................................................................. 63 2.2.2.8 Data processing ......................................................................... 64 2.2.3 Results and discussion ............................................................................. 64 2.2.4 Conclusion ............................................................................................... 72 2.3 Kendrick mass defect (KMD) ............................................................................. 74 2.3.1 Introduction ............................................................................................. 74 2.3.2 Methods
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