Cover Page The handle http://hdl.handle.net/1887/28970 holds various files of this Leiden University dissertation. Author: Raterink, Robert-Jan Title: High-throughput profiling of small molecules using mass spectrometry Issue Date: 2014-10-01 High-Throughput Profiling of Small Molecules using Mass Spectrometry Proefschrift ter verkrijging van de graad van Doctor aan d­­e Universiteit Leiden op gezag van Rector Magnificus prof. mr. C.J.J.M. Stolker, volgens besluit van College voor Promoties te verdedigen op woensdag 1 oktober 2014 klokke 13:45 uur door Robert-Jan Raterink geboren te Dronten in 1982 Promotiecommissie: Promotor: Prof. dr. Thomas Hankemeier Co-promotor: Dr. Rob Vreeken Overige leden: Prof. dr. Albert van den Berg (Twente University) Dr. Christa Cobbaert (LUMC, Leiden) Prof. dr. Meindert Danhof (Leiden University) Prof. dr. Robert Kennedy (University of Michigan) Prof. dr. Dirk Jan Reijngoud (University of Groningen) Prof. dr. Herman Spaink (Leiden University) This study was financed by the research programme of the Netherlands Metabolomics Centre (NMC) which is a part of The Netherlands Genomics Initiative/Netherlands Organization for Scientific Research. Publication of this thesis was financially supported by ZF-Screens B.V. Cover illustration: Gilberto Gennero Printed by Ipskamp Drukkers B.V. High-throughput profiling of small molecules using mass spectrometry RJ Raterink PhD thesis, Leiden University ISBN: 978-90-74538-86-2 Table Of Contents Chapter 1 Chapter 2 General Introduction 5 Recent Developments in Sample Pretreatment 13 Techniques for Mass Spectrometry-based Metabolomics Chapter 3 Rapid Metabolic Screening of Early Zebrafish Embryogenesis based on Direct-Infusion-nanoESI-FTMS 33 Chapter 4 Three-Phase Electroextraction: a New (Online) Sample Purification and Enrichment Method for Bioanalysis 47 Chapter 5 Gas Pressure Assisted Micro-Liquid-Liquid Extraction 63 coupled Online to Direct Infusion Mass Spectrometry: a New Automated Screening Platform for Bioanalysis. Chapter 6 Testing Tuberculosis Drug Efficacy in a Zebrafish High- Throughput Translational Medicine Screen 77 Chapter 7 Conclusions and Perspectives Samenvatting 97 101 Appendix Dankwoord Curriculum Vitae List of publications 105 106 107 108