Temporal and spatial variation in pharmaceutical concentrations in an urban river system
Graphical abstract
Introduction
Determining pharmaceutical exposures in environmental matrices has become a substantial area of research since the 1990s (Daughton, 2016). The presence of pharmaceuticals in freshwater systems has now been documented globally, with research especially focused in Europe and North America (aus der Beek et al., 2016). Pharmaceuticals primarily enter the environment through patient use when an unmetabolised fraction is excreted and subsequently passes through wastewater treatment plants (WWTPs), which are typically not designed to remove such organic contaminants (Luo et al., 2014). Consequently, WWTPs are significant sources of pharmaceuticals to the environment (Lindholm-Lehto et al., 2016). A recent study of United Kingdom (UK) WWTPs estimated that 13% of effluent discharges could pose risks to the receiving environment regarding pharmaceutical exposures (Comber et al., 2018). Removal rates are highly variable between treatment types (Kasprzyk-Hordern et al., 2009; Luo et al., 2014), seasons (Golovko et al., 2014), and even within treatment plants themselves (Verlicchi et al., 2012). Moreover, removal rates have only been estimated for a small fraction of the total number of pharmaceuticals in use (Boxall et al., 2014) and only a few studies have reported WWTP removals in the UK specifically (Comber et al., 2018; Kasprzyk-Hordern et al., 2009, 2008). WWTP removal rates are valuable parameters, and their inclusion in occurrence modelling substantially improves the accuracy of pharmaceutical exposure predictions (Burns et al., 2017; Verlicchi et al., 2014).
The potential for, and extent of, effects posed by pharmaceutical exposure to non-target organisms, such as fish or invertebrates, is largely unknown (Vasquez et al., 2014). However, there is mounting evidence that select pharmaceuticals are having deleterious effects at environmentally relevant (i.e. real-world) concentrations. Examples of documented effects at environmentally relevant concentrations include antidepressants causing behavioural changes in fish (fluoxetine) (Mccallum et al., 2017), disruption during early development (venlafaxine) (Thompson et al., 2017), the equivalent of human side effects from exposure to the anti-diabetic drug metformin (Niemuth et al., 2015) or the feminization of wild fish populations downstream of a pharmaceutical manufacturing facility in France (Sanchez et al., 2011). It is therefore important to characterise the source and fate of pharmaceuticals in the aquatic environment to aid in risk assessment as approaches evaluating potential adverse effect concentrations emerge.
To adequately characterise the fate of pharmaceuticals in the environment, robust monitoring campaigns which include seasonal or year-long sampling covering a range of compounds at a reasonable spatial resolution are required. However, only a small number of spatiotemporal exposure studies have been performed that meet these criteria (Baker and Kasprzyk-Hordern, 2013; Daneshvar et al., 2010; Kasprzyk-Hordern et al., 2008; Paíga et al., 2016). These exposure studies are extremely valuable as they provide detailed information which can be related back to the myriad of factors (many varying both seasonally and temporally) that influence environmental concentrations of pharmaceuticals including hydrology (Kasprzyk-Hordern et al., 2008), WWTP removal efficiency (Silva et al., 2014), pharmaceutical usage (Sun et al., 2014), and in-stream removal processes (e.g. biodegradation and sorption to sediment) (Daneshvar et al., 2010; Camacho-Munoz et al., 2010; Moreno-González et al., 2014). In combination, the impact of these processes on pharmaceutical exposure and fate is largely unknown but, if better defined, could improve exposure prediction approaches and offer greater confidence, in terms of exposure, when evaluating risks that pharmaceuticals may pose to the environment.
Recently, a handful of aqueous rapid pharmaceutical determination high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) methods have been developed that achieve comparable limits of detection (LODs) to those including sample pre-concentration or clean-up (Anumol et al., 2015; Boix et al., 2015; Campos-Mãnas et al., 2017; Furlong et al., 2014; Oliveira et al., 2015). Such methods involve utilising larger than normal injection volumes (∼100 μL) to increase the likelihood of detection (Petrie et al., 2016). Removal of the extraction step reduces sample preparation time and can increase the number of samples that can be processed (highly beneficial to large spatiotemporal exposure campaigns). A significant analytical problem arising during pharmaceutical quantification is matrix effects (typically mass spectrometric ionisation enhancement or suppression). The presence of background interferences in “dirty” matrices (e.g. streams, WWTP effluent, etc.) can co-elute with target analytes and impair quantification past the point of suitability (Petrović et al., 2005). Several approaches have been attempted to reduce matrix effects including sample pre-concentration and clean-up to help isolate target pharmaceuticals (Van De Steene et al., 2006). Such pre-concentration, however, is difficult to optimise, time consuming, costly, and may also concentrate interfering analytes, thus unintentionally increasing matrix effects (Yu et al., 2012). Matrix interferences have been reported to be comparatively lower for rapid determination methods than more costly and laborious sample pre-concentration/clean-up methods (Anumol et al., 2015).
In this study, which was performed in the frame of the Innovative Medicines Initiative iPiE project on intelligent assessment of pharmaceuticals in the environment, we validate and apply a rapid determination aqueous HPLC-MS/MS method for the quantification of 33 physico-chemically diverse pharmaceuticals to a year-long surface-water exposure campaign. Monitoring was conducted during 2016 at 11 sites along the urbanised and larger River Ouse and smaller, more rural River Foss which converge within the city of York, UK (Fig. 1). The monthly sampling design provided good temporal resolution while unparalleled spatial resolution was achieved in the two contrasting river systems. In addition, influent and effluent samples from two of the WWTPs that serve the city were collected when possible and removal efficiencies estimated. Predicted exposure concentrations (PECs) were calculated for both rivers using a simple model and the model was then evaluated against annually averaged measured environmental concentrations (MECs) calculated from the monthly sampling data.
Section snippets
Study compounds
Study compounds were selected based on those previously detected in the York river system during an initial scoping study in which 95 pharmaceuticals and degradation products were surveyed (Burns et al., 2017). From these results, 32 pharmaceuticals were selected due to either their known or expected presence. An additional pharmaceutical, gabapentin, was also included in the study due to its high usage, resistance to environmental degradation, and ecotoxic potential (Herrmann et al., 2015).
Study area
The
Method performance and quality control
The method was determined to be sufficiently reproducible as assessed by the relative standard deviation of multiple injections (n = 8) during (5.5 %RSD) and across (7.5 %RSD) analysis days according to USEPA (2016) guidelines and Boix et al. (2015) where an RSD≤ 20% above the LOQ (i.e. 80 ng/L) is desirable. The limits of detections (LOD) ranged from 0.9 ng/L (carbamazepine) to 12.4 ng/L (gabapentin) and an LOD <10 ng/L was achieved for 91% of analytes (Table S5). There were no quantifiable
Conclusion
A rapid determination HPLC-MS/MS method for 33 pharmaceuticals was validated and applied in a 12-month spatiotemporal pharmaceutical exposure campaign. WWTP removal efficiency was found to be similar between CAS and trickling filter technology for the target pharmaceuticals. Pharmaceutical concentrations in two contrasting river systems that run through the city of York, UK were found to vary significantly spatially and temporally, with the greatest variation observed for paracetamol in the
Acknowledgement
The present work is funded by the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 608014 (CAPACITIE) and partly supported by the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (iPiE Grant 115635). The York Centre of Excellence in Mass Spectrometry was created thanks to a major capital investment through Science City York, supported by Yorkshire Forward, with funds from the Northern Way Initiative, and
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