UvA-DARE (Digital Academic Repository) Wastewater-based epidemiology, an analytical chemical approach for the investigation of human consumption of lifestyle chemicals Causanilles Llanes, A. Publication date 2018 Document Version Final published version License Other Link to publication Citation for published version (APA): Causanilles Llanes, A. (2018). Wastewater-based epidemiology, an analytical chemical approach for the investigation of human consumption of lifestyle chemicals. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:10 Oct 2021 Wastewater-based epidemiology, an analy cal chemical approach for the inves ga on of human consump on of lifestyle chemicals ___________ Ana Causanilles Wastewater-based epidemiology, an analytical chemical approach for the investigation of human consumption of lifestyle chemicals ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus prof. dr. ir. K. I. J. Maex ten overstaan van een door het College voor Promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel op donderdag 24 mei 2018, te 14:00 uur door Ana Causanilles Llanes geboren te Castello de la Plana, Spanje Promotiecommissie: Promotor: prof. dr. W.P. de Voogt – Universiteit van Amsterdam Copromotor: prof. dr. F.J. Hernández Hernández – Universitat Jaume I, ES Overige leden: prof. dr. ir. P.J. Schoenmakers – Universiteit van Amsterdam prof. dr. B. Kasprzyk-Hordern – University of Bath, UK prof. dr. A.C. van Asten – Universiteit van Amsterdam prof. dr. G.L. Corthals – Universiteit van Amsterdam prof. dr. A. Covaci – Universiteit Antwerpen, BE Faculteit der Natuurwetenschappen, Wiskunde en Informatica Cover design by Alfonso A. Martínez Vicente Printed by Innovació Digital Castelló, S.L.U. Causanilles, A. (2018) Wastewater-based epidemiology, an analytical chemical approach for the investigation of human consumption of lifestyle chemicals Proefschrift Universiteit van Amsterdam, FNWI, IBED, 2018 ISBN 978-94-91407-56-7 / Copyright © 2018 The work described in this thesis was carried out at KWR Watercycle Research Institute in Nieuwegein and the Institute for Biodiversity and Ecosystem Dynamics of the University of Amsterdam. It was funded by EU-ITN SEWPROF (Marie Curie-PEOPLE Grant #317205), COST Action ES1307 supported by COST (European Cooperation in Science and Technology), and the World Anti-Doping Agency (WADA). 2 A mis padres Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less. – Marie Skłodowska Curie 3 4 Table of contents Chapter 1. General introduction 7 Chapter 2. Drugs of abuse 2.1. Improving wastewater-based epidemiology to estimate cannabis use: focus on the initial aspects of the analytical procedure 29 Annex A – Supplementary information Chapter 2.1. 47 2.2. Occurrence and fate of illicit drugs and pharmaceuticals in wastewater from two wastewater treatment plants in Costa Rica 55 Annex B – Supplementary information Chapter 2.2. 83 2.3. Qualitative screening for new psychoactive substances in wastewater collected during a city festival using liquid chromatography coupled to high-resolution mass spectrometry 89 Annex C – Supplementary information Chapter 2.3. 111 Chapter 3. Erectile dysfunction drugs 3.1. Determination of phosphodiesterase type V inhibitors in wastewater by direct injection followed by liquid chromatography coupled to tandem mass spectrometry 119 Annex D – Supplementary information Chapter 3.1. 149 3.2. Success of rogue online pharmacies: sewage study of sildenafil in the Netherlands 157 Annex E – Long rapid response 161 3.3. Comparison of phosphodiesterase type V inhibitors use in eight European cities through analysis of urban wastewater 165 5 Annex F – Supplementary information Chapter 3.3. 185 Chapter 4. Doping 4.1. Wastewater-based tracing of doping use by the general population and amateur athletes 197 Annex G – Supplementary information Chapter 4.1. 223 Chapter 5. Synthesis 239 Summary 245 Samenvatting 249 Resumen 253 References 257 List of publications 279 List of author’s contributions 283 Acknowledgements 285 6 Chapter 1 General introduction The general introduction describes the background to the research presented in this thesis. It elaborates on the interest of studying population’s lifestyle habits (1.1), focusing on the use of illicit drugs and licit substances with potential for abuse (1.2), and the role of the results from the chemical analysis of wastewater as a complementary source of information in drug epidemiology (1.3). Next, an overview of the substances studied along the thesis is given (1.4). Finally, the general aim of the research and the specific objectives of each chapter are discussed (1.5). In addition, as this research was part of a Marie Curie International Training Network, a description of the project and the research secondments performed by the PhD candidate is provided (1.6). 7 1.1. Human health and lifestyle habits The health and wellbeing of a society is influenced by the social, the economic and the physical environment, as well as by each person’s individual characteristics and behavior. Factors such as (epi)genetics, income and social status, level of education, social support, access to safe water and clean air, healthy workplaces, safe houses, communities and roads, etc. play an important role. In general, individuals are unable to control their context of life, and therefore, unlikely to directly control many of those determinants of their health. However, their behavior and coping skills (how we deal with life’s stresses and challenges), or their lifestyle habits, have a direct impact on their condition. It is in this context that individuals can make their own choices, and consequences may affect not only themselves individually but also the community where they live in. The choice of certain lifestyle habits may influence human health and wellbeing. Habits such as eating a balanced diet or keeping physically active will have a good impact and improve their condition. On the other hand, habits such as smoking, drinking alcohol, computer gaming, gambling… or the abuse of certain drugs, can turn into harmful addictions. There is an intriguing controversy (that goes beyond the scope of this work) on whether these lifestyle choices that lead to addictions are truly based on the mechanism of free will or are a chronic disease of the brain (NIDA, 2008). This is because addictive substances hyper stimulate the brain’s reward system, which might eventually result in brain damage, which might affect the quality of a person’s choices. However, empirical studies exist that have shown a voluntary substance use reduction in some addicts (Heyman, 2017), which would undermine this “brain disease” theory. Regardless this interesting controversy, it can be agreed that drug addiction is a global problem with extensive consequences for human health and the world economy. 8 1.2. The size of the problem in numbers The use of illicit drugs, and the abuse of licit drugs, is increasingly becoming a worldwide trend in lifestyle that is prevalent in rich and poor countries alike. According to the United Nations Office on Drugs and Crime (UNODC) 1 in 20 adults, or a quarter of a billion people between the ages of 15 and 64 years, used at least one drug in 2014 (UNODC, 2016). The number has been stable over the past years in proportion to the global population (see Fig. 1.1. for the available prevalence data on worldwide injecting drug use), nevertheless over 29 million suffer from drug use disorders and only 1 in 6 people with drug use disorders is in treatment. Fig. 1.1. Prevalence of injecting drug use, 2014 or latest available (taken from UNODC, 2016). 9 In addition to the use of established illicit drugs, namely cocaine, cannabis or amphetamine type stimulants, the expansion of a “new” group of substances known as new psychoactive substances (NPS, also known as designer drugs or “legal highs”), has arisen more attention in recent years. NPS are substances that are not directly controlled by international conventions (Malcolm Reid and Thomas, 2016). They are produced by introducing slight modifications to chemical structures of controlled substances and are expected to mimic the effects of illicit substances. They may pose a public health threat because very little is known about their pharmacokinetics, recommended dose, effects or safety. Furthermore, they are easily acquired through the Internet and smart shops where they are sold under various product labels with often misleading information. Every year new substances are reported to the Early Warning System (EWS) at the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). In 2015, 98 NPS were detected for the first time, bringing the number of new substances monitored to more than 560 (EMCDDA, 2016a). This trend can be seen in Fig. 1.2. Data on the prevalence of these NPS is still scarce due to the rapid changes in the market to avoid criminalization, that typically happen before a significant user base becomes established. Fig. 1.2. Number and categories of new psychoactive substances notified to the EU Early Warning System for the first time, 2009 – 15 (taken from EMCDDA, 2016a).