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Simultaneous Detection of Drugs of Abuse in Waste Water Using Gas Chromatography-Mass Spectrometry

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Simultaneous Detection of Drugs of Abuse in Waste Water Using Gas Chromatography-Mass Spectrometry ANGLIA RUSKIN UNIVERSITY Simultaneous Detection of Drugs of Abuse in Waste Water Using Gas Chromatography-Mass Spectrometry ELLEN MUSILI MWENESONGOLE A thesis in partial fulfilment of the requirements of Anglia Ruskin University for the degree of Doctor of Philosophy Submitted: January 2015 DECLARATION I DECLARE THAT THIS RESEARCH IS MY ORIGINAL WORK EXCEPT WHERE REFERENCES AND ACKNOWLEDGEMENTS ARE MADE ACKNOWLEDGEMENTS First and foremost, the author acknowledges the Department of Life Sciences at Anglia Ruskin University and the National Research Foundation of South Africa. This research would not have been possible without their financial support. I would like to thank my Director of Studies, Dr Lata Gautam, for her guidance and support through my studies and removing barriers when needed. Thanks for being open to alternative approaches to laboratory work and writing and for always smiling even at times when others would have been frowning. I also want to thank my second supervisor, Dr Sarah Hall, for valuable feedback on my work. To my advisor, Prof John Waterhouse, thank you for believing in my capabilities from the proposal stage until the end and for your very encouraging words and feedback. Your presence on the supervisory team was highly appreciated. Sincere gratitude is also expressed towards Dr Sheila Parkhurst (HOD) for putting the relevant resources towards research that enabled me to complete my work and disseminate it at conferences, and to Rev. Nigel Cooper for ‘lending an ear’ when needed and valuable advice. To my wonderful parents Prof M. and Dr E. Mwenesongole (my unofficial advisors), in whose footsteps I gladly followed and for your unconditional love, support, prayers, encouragement and ensuring I stayed calm and focused through the ups and downs. You once told me as a 10 year old to, ‘work hard at school and get good grades as this will open doors that even money can’t open’; and oh my, the doors that have been opened since then. I also want to thank my wonderful siblings and friends from South Africa, Scotland, Canada and Cambridge, and the ‘Kingsgate posse’, who prayed for and encouraged me through my studies and ensured I maintained the right social and academic balance. To fellow students in Mel 210, thanks for interesting conversations and useful feedback when needed. I would also like to thank Joanne Hooson and Kevin Bright for their technical support. I am also grateful to Rick Mister, Gosia Niewiadomska and Rosie Felton from Anglian Water for supplying water samples, on which this research relied on, and taking me on tours of the waste water treatment plant in Cambridge and the Anglian Water labs in Huntingdon. I dedicate this thesis to all my nieces and nephews and hope one or more of you will carry on the scientific baton and ‘contribute to new knowledge’ no matter how big or small. Psalms 139; Isaiah 26:3; Romans 8:28 i ANGLIA RUSKIN UNIVERSITY ABSTRACT FACULTY OF SCIENCE AND TECHNOLOGY DOCTOR OF PHILOSOPHY SIMULTANEOUS DETECTION OF DRUGS OF ABUSE IN WASTE WATER USING GAS CHROMATOGRAPHY-MASS SPECTROMETRY Ellen Musili Mwenesongole January 2015 Sewage epidemiology is increasingly becoming an alternative method of estimating drug usage and consumption patterns for a given population. With the constant emergence of new psychoactive substances such as cathinones and piperazines, versatile, reliable, specific and sensitive analytical methods are needed for their detection in complex matrices such as waste water. This thesis reports the development of an analytical method based on solid phase extraction, derivatization with pentafluoropropionic anhydride and analysis by gas chromatography-mass spectrometry for the simultaneous analysis of 29 illicit and therapeutic drugs of abuse. All 29 drugs could be reliably identified in spiked waste water samples using selected ion monitoring and splitless injection. Recoveries for the majority of the drugs were above 70 %. Linearity varied based on the analyte but was assessed in the range 2.0 x 10-4 to 1.4 µg/mL. Intra-assay and intermediate precision of the instrument was determined at 0.005, 0.1 and 1.0 µg/mL, with the majority of relative standard deviations less than 10 %. Limits of detection and quantification for drugs such as amphetamine and methamphetamine were better than reported values for liquid chromatography-tandem mass spectrometry, a more commonly used technique. Untreated 72 h composite waste water samples from Cambridge, UK, were analysed using a six-point standard addition curve. Eleven drugs of abuse were detected, including amphetamine, methamphetamine, butylone and 4-fluoromethamphetamine. The latter two having been detected for the very first time in waste water. Using the validated method, the consumption of heroin, ketamine, cocaine, methamphetamine and amphetamine, in Cambridge, UK, was estimated to be 399.4 ± 90.8, 2463.5 ± 182.5, 195.5 ± 95.4, 84.3 ± 59.1 and 38.9 ± 24.8 mg/day per 1000 inhabitants. This is the first reported validated method for the detection of both classic drugs of abuse and new psychoactive substances in waste water using gas chromatography-mass spectrometry and derivatization with pentafluoropropionic anhydride. Keywords: Drugs of abuse, gas chromatography-mass spectrometry, waste water, pentafluoropropionic anhydride, selected ion monitoring ii CONTENTS ACKNOWLEDGEMENTS i ABSTRACT ii TABLE OF CONTENTS iii APPENDICES vii LIST OF FIGURES viii LIST OF TABLES xi LIST OF ABBREVIATIONS xiv CHAPTER ONE THEORETICAL BACKGROUND TO THE RESEARCH _________________________ 1 1.1 WATER POLLUTANTS 1 1.2 SUSTAINABLE WATER MANAGEMENT 2 1.2.1 Policies Governing Sustainable Water Management 3 1.3 WATER TREATMENT 4 1.3.1 Domestic Water Treatment 4 1.3.2 Waste Water and its Composition 5 1.3.3 Waste Water Treatment 6 1.3.3.1 Preliminary Treatment 6 1.3.3.2 Primary Treatment 6 1.3.3.3 Secondary Treatment 7 1.3.3.4 Tertiary Treatment 7 1.3.4 Pharmaceuticals and Personal Care Products (PPCPs) in Waste Water 8 1.3.4.1 Pharmaceutically Active Compounds (PhACs) 9 1.3.4.2 In-Sewer Degradation and Transformation of Pharmaceuticals 11 1.3.4.3 Removal of Pharmaceuticals during Waste Water Treatment 12 1.3.4.4 Drugs of Abuse and Sewage Epidemiology 14 1.4 DRUGS OF ABUSE 16 1.4.1 Commonly Abused Abuse 17 1.4.2 Selection of Drugs for this Research 18 1.4.2.1 New Psychoactive Substances (NPS) 23 1.4.3 Linking Drug Metabolism and Sewage Epidemiology 25 1.4.4 Linking Drug Detection Levels with Consumption 27 1.5 SAMPLE COLLECTION, PRE-TREATMENT AND ANALYSIS 28 1.5.1 Water Sources and Sampling 29 1.5.2 Sample Pre-treatment and Storage 30 1.5.3 Sample Extraction 31 1.5.3.1 Solid Phase Extraction (SPE) 32 1.5.3.1.1 Oasis® Mixed-Mode Sorbents 33 1.5.3.2 Liquid-Liquid Extraction (LLE) 36 1.5.3.3 Comparison between SPE and LLE 38 1.6 CHEMICAL DERIVATIZATION 41 1.6.1 To Derivatize or Not? 41 iii 1.6.2 Silylation 45 1.6.3 Acylation 46 1.6.4 Evaluating the Derivatization Reaction 47 1.7 INSTRUMENTAL ANALYSIS 48 1.7.1 Advances in Instrumental Techniques 49 1.7.2 Mass Spectrometry 50 1.7.3 Comparison between GC-MS and LC-MS 50 1.8 VALIDATION OF AN ANALYTICAL METHOD 57 1.8.1 Key Performance Tests 58 1.8.2 Quantification by Standard Addition 59 1.9 AIM OF THE RESEARCH 60 CHAPTER TWO EXPERIMENTAL PROCEDURES _____________ 61 2.1 DRUG STANDARDS, CHEMICALS AND SOLVENTS 61 2.2 SAMPLE COLLECTION AND PREPARATION 64 2.3 GAS CHROMATOGRAPHY-MASS SPECTROMETRY (GC-MS) 65 2.4 PRELIMINARY INVESTIGATIONS 66 2.4.1 Chemical Derivatization 66 2.4.1.1 Comparison of Derivatizing Reagents 66 2.4.1.2 Optimisation of PFPA Derivatization Reactions 67 2.4.1.3 Derivatization Reactions for a Mixed Opiate Standard 67 2.4.1.4 Individual Analysis of MOR, 6-MAM and Heroin 68 2.4.2 Stability Studies 68 2.4.3 Analyte Extraction Methods 70 2.4.3.1 Liquid-liquid Extraction (LLE) 70 2.4.3.1.1 Selection of Extraction Solvent 70 2.4.3.1.2 Optimisation of pH 71 2.4.3.2 Solid Phase Extraction (SPE) 71 2.4.3.2.1 Comparison of the SPE Sorbents, Oasis® MCX and HLB 71 2.4.3.2.2 Comparison of Elution Solvents for MCX at pH 2.0 72 2.5 METHOD VALIDATION STUDIES 73 2.5.1 Instrumental Linear Range 73 2.5.2 Precision (Intra-assay and Intermediate) 74 2.5.3 Instrumental Detection and Quantification Limits 74 2.5.4 SPE Extraction and Recovery Using Optimised Instrumental Method 74 2.5.5 Matrix-based Stability 75 2.5.6 Standard Addition 75 2.6 SYSTEM SUITABILITY TESTS (SST) AND QUALITY CONTROL (QC) 75 CHAPTER THREE RESULTS AND DISCUSSION – PRELIMINARY STUDIES ______ 77 3.1 INTRODUCTION 77 3.2 CHEMICAL DERIVATIZATION 77 3.2.1 Comparison of Derivatizing Reagents 78 iv 3.2.2 Optimisation of PFPA Derivatization Reactions 90 3.2.3 Derivatization Reactions for a Mixed Opiate Standard 94 3.2.3.1 Individual Analysis of MOR, 6-MAM and Heroin 98 3.2.4 Final Derivatization Conditions 100 3.2.5 Diagnostic Ions and Mass Spectra 100 3.2.5.1 Peak Separation and Isomers 103 3.2.6 PFPA Derivatives - Novel in Sewage Epidemiology 105 3.3 STABILITY STUDIES 106 3.3.1 27 hour Autosampler Stability of a Derivatized Mixed Standard 106 3.3.2 4 Week Storage Stability of a Derivatized Mixed Standard 109 3.3.3 4 Week Storage Stability of an Underivatized Mixed Standard 112 3.4 ANALYTE EXTRACTION METHODS 116 3.4.1 Liquid-Liquid Extraction (LLE) 116 3.4.1.1 Selection of Solvent 116 3.4.1.2 Optimisation of pH 119 3.4.2 Solid Phase Extraction (SPE) 121 3.4.2.1 Comparison of the SPE sorbents, Oasis® MCX and HLB 121 3.4.2.2 Comparison of Elution Solvents for MCX at pH 2.0 127 3.4.3 Selectivity through Extraction and Recovery 130 3.4.4
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