Investigation of drugs of abuse and relevant metabolites in Dutch sewage water by liquid chromatography coupled to high resolution mass spectrometry

An extensive study on the presence of illicit drugs and pharmaceuticals with potential for abuse in sewage waters was made for the first time in the Netherlands. A total number of 24 target drugs were investigated in influent and effluent wastewater using liquid chromatography coupled to a high resolution Orbitrap mass spectrometer. This powerful analyzer has allowed not only the detection and identification of the compounds under investigation, but also their quantification at very low levels, which is highly innovative in the field of drugs of abuse. Samples were taken from five sewage treatment plants (STPs) during a whole week. The selected STPs served four cities of different size and an international airport. Daily variances of drug loads were demonstrated and removal efficiencies calculated for each drug and STP individually. Twelve target compounds were found in at least one influent or effluent, and highest concentrations were observed in influents collected from more urbanized areas. The compounds more frequently detected were amphetamine, benzoylecgonine, cocaine and THCsingle bondCOOH together with the pharmaceuticals codeine, oxazepam and temazepam. Established week trends in consumption of drugs showed distinct differences between individual drugs. A slightly different occurrence pattern was observed in wastewaters from the airport. Thus, methamphetamine was only detected at Schiphol, a fact that was interpreted to be caused by consumption of this drug by travelers. Despite the fact that the Netherlands has frequently been criticized for its liberal drug policy the results from this study did not reveal higher drug consumption than found elsewhere, with the exception of cannabis

Sewage epidemiology and illicit drug research: the development of ethical research guidelines

Aims: To discuss the need to develop ethical guidelines for researchers using sewage epidemiology to monitor drug use in the general population and specific precincts, including prisons, schools and workplaces

High Resolution Mass Spectrometry of Polyfluorinated Polyether-Based Formulation

High resolution mass spectrometry (HRMS) was successfully applied to elucidate the structure of a polyfluorinated polyether (PFPE)-based formulation. The mass spectrum generated from direct injection into the MS was examined by identifying the different repeating units manually and with the aid of an instrument data processor. Highly accurate mass spectral data enabled the calculation of higher-order mass defects. The different plots of MW and the nth-order mass defects (up to n = 3) could aid in assessing the structure of the different repeating units and estimating their absolute and relative number per molecule. The three major repeating units were -C2H4O-, -C2F4O-, and -CF2O-. Tandem MS was used to identify the end groups that appeared to be phosphates, as well as the possible distribution of the repeating units. Reversed-phase HPLC separated of the polymer molecules on the basis of number of nonpolar repeating units. The elucidated structure resembles the structure in the published manufacturer technical data. This analytical approach to the characterization of a PFPE-based formulation can serve as a guide in analyzing not just other PFPE-based formulations but also other fluorinated and non-fluorinated polymers. The information from MS is essential in studying the physico-chemical properties of PFPEs and can help in assessing the risks they pose to the environment and to human health

Facilitating high resolution mass spectrometry data processing for screening of environmental water samples: An evaluation of two deconvolution tools

A screening approach was applied to influent and effluent wastewater samples. After injection in a LC-LTQ-Orbitrap, data analysis was performed using two deconvolution tools, MsXelerator (modules MPeaks and MS Compare) and Sieve 2.1. The outputs were searched incorporating an in-house database of more than 200 pharmaceuticals and illicit drugs or ChemSpider. This hidden target screening approach led to the detection of numerous compounds including the illicit drug cocaine and its metabolite benzoylecgonine and the pharmaceuticals carbamazepine, gemfibrozil and losartan. The compounds found using both approaches were combined, and isotopic pattern and retention time prediction were used to filter out false positives. The remaining potential positives were reanalysed in MS/MS mode and their product ions were compared with literature and/or mass spectral libraries. The inclusion of the chemical database ChemSpider led to the tentative identification of several metabolites, including paraxanthine, theobromine, theophylline and carboxylosartan, as well as the pharmaceutical phenazone. The first three of these compounds are isomers and they were subsequently distinguished based on their product ions and predicted retention times. This work has shown that the use deconvolution tools facilitates non-target screening and enables the identification of a higher number of compoundsRichard Bade and Ana Causanilles acknowledge the European Union for their Early Stage Researcher (ESR) contracts as part of the EU-International Training Network SEWPROF (Marie Curie- PEOPLE Grant #317205) Part of this work was supported by the COST Action ES1307 “SCORE - Sewage biomarker analysis for community health assessment”. The financial support of Generalitat Valenciana (Prometeo II 2014/023) and of the Spanish Ministry of Economy and Competitiveness (Project ref CTQ2015-65603) is also acknowledged by the authors of University Jaume I

Non-target screening reveals time trends of polar micropollutants in a riverbank filtration system

The historic emissions of polar micropollutants in a natural drinking water source were investigated by nontarget screening with high-resolution mass spectrometry and open cheminformatics tools. The study area consisted of a riverbank filtration transect fed by the river Lek, a branch of the lower Rhine, and exhibiting up to 60-year travel time. More than 18,000 profiles were detected. Hierarchical clustering revealed that 43% of the 15 most populated clusters were characterized by intensity trends with maxima in the 1990s, reflecting intensified human activities, wastewater treatment plant upgrades and regulation in the Rhine riparian countries. Tentative structure annotation was performed using automated in silico fragmentation. Candidate structures retrieved from ChemSpider were scored based on the fit of the in silico fragments to the experimental tandem mass spectra, similarity to openly accessible accurate mass spectra, associated metadata, and presence in a suspect list. Sixty-seven unique structures (72 over both ionization modes) were tentatively identified, 25 of which were confirmed and included contaminants so far unknown to occur in bank filtrate or in natural waters at all, such as tetramethylsulfamide. This study demonstrates that many classes of hydrophilic organics enter riverbank filtration systems, persisting and migrating for decades if biogeochemical conditions are stable

Transformation and sorption of illicit drug biomarkers in sewer systems: understanding the role of suspended solids in raw wastewater

Sewer pipelines, although primarily designed for sewage transport, can also be considered as bioreactors. In-sewer processes may lead to significant variations of chemical loadings from source release points to the treatment plant influent. In this study, we assessed in-sewer utilization of growth substrates (primary metabolic processes) and transformation of illicit drug biomarkers (secondary metabolic processes) by suspended biomass. Sixteen drug biomarkers were targeted, including mephedrone, methadone, cocaine, heroin, codeine, and tetrahydrocannabinol (THC) and their major human metabolites. Batch experiments were performed under aerobic and anaerobic conditions using raw wastewater. Abiotic biomarker transformation and partitioning to suspended solids and reactor wall were separately investigated under both redox conditions. A process model was identified by combining and extending the Wastewater Aerobic/anaerobic Transformations in Sewers (WATS) model and Activated Sludge Model for Xenobiotics (ASM-X). Kinetic and stoichiometric model parameters were estimated using experimental data via the Bayesian optimization method DREAM(ZS). Results suggest that biomarker transformation significantly differs from aerobic to anaerobic conditions, and abiotic conversion is the dominant mechanism for many of the selected substances. Notably, an explicit description of biomass growth during batch experiments was crucial to avoid significant overestimation (up to 385%) of aerobic biotransformation rate constants. Predictions of in-sewer transformation provided here can reduce the uncertainty in the estimation of drug consumption as part of wastewater-based epidemiological studies

Removal of polar organic micropollutants by pilot-scale reverse osmosis drinking water treatment

The robustness of reverse osmosis (RO) against polar organic micropollutants (MPs) was investigated in pilot-scale drinking water treatment. Experiments were carried in hypoxic conditions to treat a raw anaerobic riverbank filtrate spiked with a mixture of thirty model compounds. The chemicals were selected from scientific literature data based on their relevance for the quality of freshwater systems, RO permeate and drinking water. MPs passage and the influence of permeate flux were evaluated with a typical low-pressure RO membrane and quantified by liquid chromatography coupled to high-resolution mass spectrometry. A strong inverse correlation between size and passage of neutral hydrophilic compounds was observed. This correlation was weaker for moderately hydrophobic MPs. Anionic MPs displayed nearly no passage due to electrostatic repulsion with the negatively charged membrane surface, whereas breakthrough of small cationic MPs could be observed. The passage figures observed for the investigated set of MPs ranged from less than 1%-25%. Statistical analysis was performed to evaluate the relationship between physicochemical properties and passage. The effects of permeate flux were more pronounced for small neutral MPs, which displayed a higher passage after a pressure drop

Characterization of aggregates of surface modified fullerenes by asymmetrical flow field-flow fractionation with multi-angle light scattering detection

Fullerenes are carbon nanoparticles with widespread biomedical, commercial and industrial applications. Attributes such as their tendency to aggregate and aggregate size and shape impact their ability to be transported into and through the environment and living tissues. Knowledge of these properties is therefore valuable for their human and environmental risk assessment as well as to control their synthesis and manufacture. In this work, asymmetrical flow-field flow fractionation (AF4) coupled to multi-angle light scattering (MALS) was used for the first time to study the size distribution of surface modified fullerenes with both polyhydroxyl and carboxyl functional groups in aqueous solutions having different pH (6.5-11) and ionic strength values (0-200 mM) of environmental relevance. Fractionation key parameters such as flow rates, flow programming, and membrane material were optimized for the selected fullerenes. The aggregation of the compounds studied appeared to be indifferent to changes in solution pH, but was affected by changes in the ionic strength. Polyhydroxy-fullerenes were found to be present mostly as 4 nm aggregates in water without added salt, but showed more aggregation at high ionic strength, with an up to 10-fold increase in their mean hydrodynamic radii (200 mM), due to a decrease in the electrostatic repulsion between the nanoparticles. Carboxy-fullerenes showed a much stronger aggregation degree in water (50 100 nm). Their average size and recoveries decreased with the increase in the salt concentration. This behavior can be due to enhanced adsorption of the large particles to the membrane at high ionic strength, because of their higher hydrophobicity and much larger particle sizes compared to polyhydroxy-fullerenes. The method performance was evaluated by calculating the run-to-run precision of the retention time (hydrodynamic radii), and the obtained RSD values were lower than 1 %. MALS measurements showed aggregate sizes that were in good agreement with the AF4 data. A comparison of the scattering radii from the MALS with the hydrodynamic radii obtained from the retention times in AF4 indicated that the aggregate shapes are far from spherical. TEM images of the fullerenes in the dry state also showed branched and irregular clusters