University of Groningen Screening of Doping Substances in Human Urine with Gas and Liquid Chromatography Coupled to High-Resolution Mass Spectrometry Abushareeda, Wadha DOI: 10.33612/diss.131230681 IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2020 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Abushareeda, W. (2020). Screening of Doping Substances in Human Urine with Gas and Liquid Chromatography Coupled to High-Resolution Mass Spectrometry. 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For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 08-10-2021 Screening of Doping Substances in Human Urine with Gas and Liquid Chromatography Coupled to High­ Resolution Mass Spectrometry PhD thesis Wadha Abushareeda The author gratefully thanks Groningen University and Anti­Doping Laboratory Qatar for facilitating and supportingtheresearch. The research described in this thesis was financially supported by Qatar National Research Fund (QNRF) NPRP:6­334­3­087, Doha, Qatar. Cover picture: http://www.adlqatar.qa/ Cover layout: Wadha Abushareeda Cover design: Aspire Printing, www.aspireprinting.qa Printed by: Proefschriftmaken, www.proefschriftmaken.nl ©2020, Wadha Abushareeda All rights reserved. No parts of this thesis may be reproduced or transmitted in any form, by any means, without prior written permission from the author. Screening of Doping Substances in Human Urine with Gas and Liquid Chromatography Coupled to High­ Resolution Mass Spectrometry PhD thesis to obtain the degree of PhD at the University of Groningen on the authority of the Rector Magnificus Prof. C. Wijmenga and in accordance with the decision by the College of Deans. This thesis will be defended in public on Monday 7 September 2020 at 9.00 hours by Wadha Abushareeda born on 19 August 1980 in Doha, Qatar Supervisors Prof. P.L. Horvatovich Dr. C. Georgakopoulos Assessment Committee Prof. H.J. Haisma Prof. D.J. Touw Prof. F. Botrè This Thesis is dedicated to my husband Table of Contents List of abbreviations ................................................................................................................................. 11 Chapter 1 ................................................................................................................................................... 15 General Introduction and Outline of The Thesis ................................................................................... 15 1.1 General Introduction ......................................................................................................................... 17 1.2 Thesis Outline ................................................................................................................................... 21 Chapter 2 ................................................................................................................................................... 27 Advances in the Detection of Designer Steroids in the Anti-Doping .................................................... 27 Abstract ................................................................................................................................................... 28 2.1 Introduction ....................................................................................................................................... 29 2.2 The Past and Present of The Designer AAS ..................................................................................... 31 2.3 Authorities Against Illegal Laboratories ........................................................................................... 33 2.4 Designer Synthetic AAS–The Chemistry ......................................................................................... 34 2.5 Endogenous Designer AAS .............................................................................................................. 38 2.6 Detection of Designer AAS .............................................................................................................. 39 2.7 Data processing ................................................................................................................................. 43 2.8 RNA-sequencing ............................................................................................................................... 44 2.9 Synthesis of Metabolites of Designer AAS ...................................................................................... 44 2.10 Animal Doping with Designer AAS ............................................................................................... 46 2.11 Anti-Doping Samples Preservation: Urine Stabilization, Blood Spots ........................................... 46 2.12 Conclusion ...................................................................................................................................... 48 Acknowledgments ................................................................................................................................... 48 References ............................................................................................................................................... 49 Chapter 3 ................................................................................................................................................... 57 High-Resolution Full Scan Liquid Chromatography Mass Spectrometry Comprehensive Screening in Sports Antidoping Urine Analysis ....................................................................................................... 57 Abstract ................................................................................................................................................... 58 3.1 Introduction ....................................................................................................................................... 59 3.2. Materials and Methods ..................................................................................................................... 61 3.3 Result and discussion ........................................................................................................................ 65 3.4 Conclusion ........................................................................................................................................ 83 Acknowledgment .................................................................................................................................... 83 References ............................................................................................................................................... 84 Chapter 4 ................................................................................................................................................... 87 7 Gas Chromatographic Quadrupole Time-of-Flight Full Scan High- Resolution Mass Spectrometric Screening of Human Urine in Antidoping Analysis ............................................................................... 87 4.1 Introduction ....................................................................................................................................... 89 4.2. Material and Methods ...................................................................................................................... 91 4.3. Result and Discussion ...................................................................................................................... 94 4.4. Conclusions .................................................................................................................................... 106 Acknowledgements ............................................................................................................................... 107 References ............................................................................................................................................. 108 Chapter 5 ................................................................................................................................................. 111 Comparison of Gas Chromatography Quadrupole Time-Of-Flight and Quadrupole Orbitrap Mass Spectrometry in Anti-doping Analysis: I. Detection of Anabolic-androgenic Steroids .................... 111 Abstract ................................................................................................................................................