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 THCCOOH 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.     

Occurrence and removal of pharmaceuticals in wastewater treatment plants at the Spanish Mediterranean area of Valencia

A survey on the presence of pharmaceuticals in urban wastewater of a Spanish Mediterranean area (Castellon province) was carried out. The scope of the study included a wide variety of pharmaceuticals belonging to different therapeutical classes. For this purpose, 112 samples, including influent and effluent wastewater, from different conventional wastewater treatment plants were collected. Two monitoring programmes were carried out along several seasons. The first was in June 2008 and January 2009, and the second in April and October 2009. During the first monitoring, the occurrence of 20 analytes in 84 urban wastewater samples (influent and effluent) was studied. The selection of these pharmaceuticals was mainly based on consumption. From these, 17 compounds were detected in the samples, with analgesics and anti-inflammatories, cholesterol lowering statin drugs and lipid regulators being the most frequently detected groups. 4-Aminoantipyrine, bezafibrate, diclofenac, gemfibrozil, ketoprofen, naproxen and venlafaxine were the compounds most frequently found. In the highlight of these results, the number of analytes was increased up to around 50. A lot of antibiotic compounds were added to the target list as they were considered “priority pharmaceuticals” due to their more potential hazardous effects in the aquatic environment. Data obtained during the second monitoring programme (spring and autumn) corroborated the results from the first one (summer and winter). Analgesics and anti-inflammatories, lipid regulators together with quinolone and macrolide antibiotics were the most abundant pharmaceuticals. Similar median concentrations were found over the year and seasonal variation was not clearly observed. The removal efficiency of pharmaceuticals in the wastewater treatment plants was roughly evaluated. Our results indicated that elimination of most of the selected compounds occurred during the treatment process of influent wastewater, although it was incomplete.     

The occurrence of antihistamines in sewage waters and in recipient rivers

Background, aim and scope  Each year, large quantities of pharmaceuticals are consumed worldwide for the treatment and prevention of human and animal diseases. Although the drugs and the metabolites observed in the wastewaters and in the environment are present at concentrations several orders of magnitude lower than the concentrations required to exert their effects in humans or animals, their long-term impact on the environment is commonly not known. In this study, the occurrence of six antihistamines, which are used for the relief of allergic reactions such as hay fever, was determined in sewage treatment plants wastewaters and in recipient river waters. Materials and methods  The occurrence of the antihistamines cetirizine, acrivastine, fexofenadine, loratadine, desloratadine and ebastine in sewage treatment plants wastewaters and in recipient river waters was studied. The analytical procedure consisted of solid-phase extraction of the water samples followed by liquid chromatography separation and detection by a triple-quadrupole mass spectrometer in the multiple reaction mode. Results  Cetirizine, acrivastine and fexofenadine were detected in both influent and effluent wastewater samples at concentration levels ranging from about 80 to 220 ng/L, while loratadine, desloratadine and ebastine could not be detected in any samples. During sewage treatment, the concentration of the antihistamines dropped by an average of 16–36%. Furthermore, elevated concentrations of antihistamines were observed in samples collected during the season of most intensive plant pollen production, i.e. in May. In the river water samples, the relative pattern of occurrence of cetirizine, acrivastine and fexofenadine was similar to that in the wastewater samples; although the concentration of the compounds was substantially lower (4–11 ng/L). The highest concentrations of the studied drugs were observed near the discharging point of the sewage treatment plant. Discussion  The highest concentrations of antihistamines in STP wastewaters correlate with the outbreak of allergic reaction caused by high amounts of plant pollens in the air. The analysis results of the river water samples show that the antihistamines are carried far away from the effluent discharge points. They may account for a part of the mix of pharmaceuticals and of pharmaceutical metabolites that occur downstream of STPs. Conclusions  Antihistamines are poorly degraded/eliminated under the biological treatment processes applied in the wastewater treatment plants and, consequently, they are continuously being discharged along with other drugs to the aquatic environment. Recommendations and perspectives  As a huge quantity and variety of drugs and their metabolites are continuously discharged to rivers and the sea, the compounds should be considered as contaminants that may possess risks to the aquatic ecosystem. Further studies are urgently needed on the environmental fate of the antihistamines and other pharmaceuticals in the aquatic environment. These studies should be concerned with the stability of the compounds, their transformation reactions and the identity of the transformation products, the distribution of drugs and their uptake and effects in organisms. On the basis of these studies, the possible environmental hazards of pharmaceuticals may be assessed.     

Modelling of pharmaceutical residues in Australian sewage by quantities of use and fugacity calculations

A conceptual model is presented for determining which currently prescribed pharmaceutical compounds are most likely to be found in sewage, and for estimating their concentrations, both in raw sewage and after successive stages of secondary sewage treatment. A ranking of the "top-50" pharmaceutical compounds (by total mass dispensed) in Australia over the 1998 calendar year was prepared. Information on the excretion ratios and some metabolites of the pharmaceuticals enabled prediction of the overall rates of excretion into Australian sewage. Mass-balance and fugacity modelling, applied to sewage generation and to a sewage treatment plant, allowed calculation of predicted concentrations of the compounds in raw, primary and secondary treated sewage effluents. Twenty nine of the modelled pharmaceutical residuals were predicted to be present in raw sewage influent at concentrations of 1 microgl(-1) or greater. Twenty of the compounds were predicted to remain in secondary effluent at concentrations of 1 microgl(-1) or greater.     

Drugs in the environment: emission of drugs, diagnostic aids and disinfectants into wastewater by hospitals in relation to other sources--a review.

After administration, pharmaceuticals are excreted by the patients into wastewater. Unused medications are sometimes disposed of in drains. The drugs enter the aquatic environment and eventually reach drinking water if they are not biodegraded or eliminated during sewage treatment. Additionally, antibiotics and disinfectants are supposed to disturb the wastewater treatment process and the microbial ecology in surface waters. Furthermore, resistant bacteria may be selected in the aeration tanks of STPs by the antibiotic substances present. Recently, pharmaceuticals have been detected in surface water, ground water and drinking water. However, only little is known about the significance of emissions from households and hospitals. A brief summary of input by different sources, occurrence, and elimination of different pharmaceutical groups such as antibiotics, anti-tumour drugs, anaesthetics and contrast media as well as AOX resulting from hospital effluent input into sewage water and surface water will be presented.     

The arrival and discharge of conjugated estrogens from a range of different sewage treatment plants in the UK

The occurrence of free and conjugated estrogens was examined in a survey of eleven sewage treatment plants (STPs) and their discharge water in the United Kingdom using grab sampling. The STPs included trickling filter with and without tertiary treatment, and activated sludge with tertiary treatment. For three activated sludge plants both influent and effluent samples were compared. For a further 8 STPs only the effluent was examined. The estrone-3-sulphate, estradiol-3-sulphate and estriol-3-sulphate concentrations (up to 20 ng L⁻¹) were typically 5-fold that of the respective free estrogen concentration in the effluents. This represents a substantial additional ‘potential’ estrogen load arriving in the receiving waters. Estrone-3-glucuronide was found at 9 ng L⁻¹, estradiol-3-glucuronide at 7 ng L⁻¹, and estriol-3-glucuronide at 32 ng L⁻¹ in sewage influent. Except on one occasion, no glucuronide conjugates could be found in the effluent. The results suggest in most cases glucuronide conjugates will be completely transformed in sewage treatment whilst sulphate conjugates will only be partially removed.     

Considerations about the enantioselective transformation of polycyclic musks in wastewater, treated wastewater and sewage sludge and analysis of their fate in a sequencing batch reactor plant

The present work consists of two distinct parts: in the first part enantioselective GC was used to separate the different enantiomeric/diastereomeric polycyclic musks, PCMs (HHCB, AHTN, AHDI, ATII and DPMI) including the main transformation product of HHCB, HHCB-lactone, in wastewater and sewage sludge. After optimization all PCMs were resolved on a cyclodextrin containing Rt-BDEXcst capillary GC column. Enantiomeric ratios of PCMs in a technical mixture were determined and compared to those obtained from enantioselective separation of wastewater and sewage sludge samples. In general, enantiomeric ratios were similar for most materials in influent, effluent and stabilized sewage sludge. However, the ratios for HHCB, AHDI and particularly ATII suggest some stereospecific removal of these compounds. In the second part, a field study was conducted on a wastewater treatment plant comprising a sequencing batch reactor. Concentrations of HHCB, AHTN, ADBI, AHDI, ATII, DPMI and HHCB-lactone were determined by non-enantioselective GC in daily samples of influent, effluent and activated sludge during one week. Mean concentrations in influent were 6900 and 1520 ng/l for HHCB and AHTN, respectively. The other PCMs exhibited contents 200 ng/l. Mean percent removal was between 61% (AHDI) and 87% (HHCB) resulting in mean effluent concentrations below 860 ng/l. HHCB-lactone concentration increased during wastewater treatment with a mean in the influent of 430 ng/l and in the effluent of 900 ng/l, respectively, indicating a degradation of HHCB.     

Fate of selected pharmaceuticals in hospital and municipal wastewater effluent: occurrence,removal, and environmental risk assessment

The concentrations and distribution of β-blockers, lipid regulators, and psychiatric and cancer drugs in the influent and effluent of the municipal wastewater treatment plant (WWTP) and the effluent of 16 hospitals that discharge into the wastewater treatment plant mentioned in this study at two sampling dates in summer and winter were examined. The pharmaceutical contribution of hospitals to municipal wastewater was determined. The removal of target pharmaceuticals was evaluated in a WWTP consisting of conventional biological treatment using activated sludge. Additionally, the potential environmental risk for the aquatic receiving environments (salt lake) was assessed. Beta-blockers and psychiatric drugs were detected in high concentrations in the wastewater samples. Atenolol (919 ng/L) from β-blockers and carbamazepine (7008 ng/L) from psychiatric pharmaceuticals were detected at the highest concentrations in hospital wastewater. The total pharmaceutical concentration determined at the WWTP influent and effluent was between 335 and 737 ng/L in summer and between 174 and 226 ng/L in winter. The concentrations detected in hospital effluents are higher than the concentrations detected in WWTP. The total pharmaceutical contributions from hospitals to the WWTP in summer and winter were determined to be 2% and 4%, respectively. Total pharmaceutical removal in the WWTP ranged from 23 to 54%. According to the risk ratios, atenolol could pose a high risk (risk quotient > 10) for fish in summer and winter. There are different reasons for the increase in pharmaceutical consumption in recent years. One of these reasons is the COVID-19 pandemic, which has been going on for 2 years. In particular, hospitals were operated at full capacity during the pandemic, and the occurrence and concentration of pharmaceuticals used for the therapy of COVID-19 patients has increased in hospital effluent. Pandemic conditions have increased the tendency of people to use psychiatric drugs. It is thought that beta-blocker consumption has increased due to cardiovascular diseases caused by COVID-19. Therefore, the environmental risk of pharmaceuticals for aquatic organisms in hospital effluent should be monitored and evaluated.

     

Emissions of OTNE (Iso-E-super) - mass flows in sewage treatment plants

The fate and mass flows of OTNE ([1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethylnaphthalen-2yl]ethan-1-one) which is commercialized as Iso-E-Super were studied in three large scale sewage treatment plants (STPs) in detail. The results are compared to 14 smaller ones located in Germany and Switzerland. OTNE inflow concentrations ranged from 4000 to 13,000 ngl(-1) while the effluent concentrations ranged from 500 to 6,900 ngl(-1). It is eliminated from the waste water with 56-64% during waste water treatment. High OTNE concentrations in sewage sludge showed that the elimination was mainly driven by sorption to sludge. This complies with major elimination in the first settling basins (primary settling tanks) while it was removed to a lesser extent in the aeration basin of the activated sludge treatment or in successive biofilters. The mass flows of OTNE in the influent of the German STPs were between 0.9 and 1.9 g per inhabitant and year. In the annual effluents mass flows of OTNE ranged between 0.2 and 0.8 g per inhabitant which complies with data measured in 13 smaller STPs from Switzerland. The similarity of data suggests that the observed mass flow data might be extrapolated to other European regions.     

What difference might sewage treatment performance make to endocrine disruption in rivers?

An assessment of the steroid estrogen removing performance of 23 different sewage treatment plants (STPs) was performed. The assessment relied on a model to estimate influent concentrations, and completed questionnaires on the STP treatment details from the relevant water companies. This information was compared with observed effluent 17beta-estradiol (E2) and estrone (E1) concentrations. The 10 biological filter plants (BFP) in the study performed poorly with only 30% (SD 31) removal on average for E1. This reduced E1 removal performance of the BFPs compared to all the other STP types in the survey was statistically significant (p<0.001). Scenarios of all the STPs as activated sludge types, and one as all BFP types were modelled using the GREAT-ER model set up for the Aire/Calder catchment in the UK. This difference was shown to have an important effect on predicted river E1 concentrations and consequent risk classifications.     

Highly organic natural media as permeable reactive barriers: TCE partitioning and anaerobic degradation profile in eucalyptus mulch and compost

The occurrence, removal efficiency and seasonal variation of 22 antibiotics, including eight fluoroquinolones, nine sulfonamides and five macrolides, were investigated in eight sewage treatment plants (STPs) in Beijing, China. A total of 14 antibiotics were detected in wastewater samples, with the maximum concentration being 3.1 μg L⁻¹ in the influent samples and 1.2 μg L⁻¹ in the effluent samples. The most frequently detected antibiotics were ofloxacin, norfloxacin, sulfadiazine, sulfamethoxazole, erythromycin and roxithromycin; of these, the concentration of ofloxacin was the highest in most of the influent and effluent samples. Eighteen antibiotics were detected in the sludge samples, with concentrations ranging from 1.0 × 10⁻¹ to 2.1 × 10⁴ μg kg⁻¹. The dominant antibiotics found in the sludge samples were the fluoroquinolones, with ofloxacin having the highest concentration in all the sludge samples. The antibiotics could not be removed completely by the STPs, and the mean removal efficiency ranged from −34 to 72%. Of all the antibiotics, the fluoroquinolones were removed comparatively more efficiently, probably due to their adsorption to sludge. Seasonal variation of the antibiotics in the sludge samples was also studied. The concentrations of antibiotics in winter were higher than in spring and autumn. Since the total levels of the fluoroquinolones detected in the influent samples were lower than the predicted no-effect concentration (PNEC) of 8.0 μg L⁻¹, the residues of these antibiotics would be unlikely to have adverse effects on microorganisms involved in sewage treatment processes.     

Pilot survey monitoring pharmaceuticals and related compounds in a sewage treatment plant located on the Mediterranean coast

A one-year monitoring study was performed to evaluate the occurrence, persistence and fate of a group of 14 organic compounds in a sewage treatment plant (STP) located in the south of Spain. These results are part of a more extensive study, financed by the Spanish Ministry of Research with the aim to evaluate the traceability of new pollutants on the Mediterranean coast and to determine the removal efficiency of sewage treatment plants (STP) for these pollutants. The compounds which have been analyzed include pharmaceuticals of various therapeutic categories (ibuprofen, acetaminophen, dipyrone, diclofenac, carbamazepine and codeine), pesticides (chlorfenvinfos and permethrin), caffeine, triclosan, bisphenol A and three of their more relevant metabolites (1,7-dimethylxanthine, carbamazepine 10,11-epoxide and 2,7/2,8-dichlorodibenzo-p-dioxin). An SPE/GC-MS multi-residue analytical method was developed and validated to facilitate simultaneous determination of these compounds in both influent and effluent wastewater. The method provided mean recoveries higher than 75%, with the exception of 2,7/2,8-dichlorodibenzo-p-dioxin, dipyrone and permethrin which exhibited recoveries lower than 22%. The overall variability of the method was below 14%. The method detection limit (LOD) was between 1 and 100 ng l(-1) and precision, which was calculated as relative standard deviation (RSD), ranged from 1.8% to 11.2%. The application of the proposed method has allowed the identification of all the target compounds at mean concentrations which ranged from 0.12 to 134 microg l(-1) in the influent and from 0.09 to 18.0 microg l(-1) in the effluent. The removal efficiencies of the STP for these compounds varied from 20% (carbamazepine) to 99% (acetaminophen), but in all cases resulted insufficient in order to avoid their presence in treated water and subsequently in the environment.     

The occurrence and removal of selected pharmaceutical compounds in a sewage treatment works utilising activated sludge treatment

Pharmaceutical substances have been detected in sewage effluents as well as receiving waters in many parts of the world. In this study, the occurrence and removal of a number of drug compounds were studied within a large sewage treatment plant in the south of England. Samples were processed using solid phase extraction and analysed using gas chromatography-mass spectrometry (GC-MS). The results demonstrate that ibuprofen, paracetamol, salbutamol and mefenamic acid were present in both the influent and effluent of the works while propranolol-HCl was not found above the limit of quantification in any sample. Elimination rates were circa 90% for each compound but several hundred nanograms per litre were still present in the final effluent.     

Determination of clindamycin and its metabolite clindamycin sulfoxide in diverse sewage samples

In a research project on risk management of harmful substances in water cycles, clindamycin and 12 further antibiotics were determined in different sewage samples. In contrast to other antibiotics, an increase of the clindamycin concentration in the final effluent in comparison to the influent of the sewage treatment plant (STP) was observed. A back transformation from the main metabolite clindamycin sulfoxide to clindamycin during the denitrification process has been discussed. Therefore, the concentration of this metabolite was measured additionally. Clindamycin sulfoxide was stable in the STP and the assumption of back transformation of the metabolite to clindamycin was confuted. To explain the increasing clindamycin concentration in the STP, the ratio of clindamycin sulfoxide to clindamycin was observed. The ratio increased in dry spells with concentrated samples and with long dwell time in the sewer system. A short hydraulic retention in waste water system and diluted samples in periods of extreme rainfall lead to a lower ratio of clindamycin sulfoxide to clindamycin concentration. A plausible explanation of this behavior could be that clindamycin was adsorbed strongly to a component of the sewage during this long residence time and in the STP, clindamycin was released. In the common sample preparation in the lab, clindamycin was not released. Measurements of clindamycin and clindamycin sulfoxide in the influent and effluent of STP is advised for sewage monitoring.     

Behavior of sartans (antihypertensive drugs) in wastewater treatment plants,their occurrence and risk for the aquatic environment

Pharmaceuticals and other anthropogenic trace contaminants reach wastewaters and are often not satisfactorily eliminated in sewage treatment plants. These contaminants and/or their degradation products may reach surface waters, thus influencing aquatic life. In this study, the behavior of five different antihypertonic pharmaceuticals from the sartan group (candesartan, eprosartan, irbesartan, olmesartan and valsartan) is investigated in lab-scale sewage plants. The elimination of the substances with related structures varied broadly from 17 % for olmesartan up to 96 % for valsartan. Monitoring data for these drugs in wastewater effluents of six different sewage treatment plants (STPs) in Bavaria, and at eight rivers, showed median concentrations for, e.g. valsartan of 1.1 and 0.13 μg L^?1, respectively. Predicted environmental concentrations (PEC) were calculated and are mostly consistent with the measured environmental concentrations (MEC). The selected sartans and the mixture of the five sartans showed no ecotoxic effects on aquatic organisms in relevant concentrations. Nevertheless, the occurrence of pharmaceuticals in the environment should be reduced to minimize the risk of their distribution in surface waters, ground waters and bank filtrates used for drinking water.     

Assessment of degradation of 18 antibiotics in the Closed Bottle Test

Large quantities of antibiotics are used in health care. After administration, they are discharged into the effluent and reach sewage treatment plants (STPs); if they are not degraded, they will eventually enter the environment. Antibiotics can affect bacteria in the environment and thus disturb natural elemental cycles. For this reason, it is necessary to take a closer look at the fate and effects of these substances in the environment. The biodegradability of 18 clinically important antibiotics and their effects on environmental bacteria was studied using the Closed Bottle Test (CBT) (OECD 301 D 1992). In addition, a toxicity control was performed in the CBT and the colony forming units (CFUs) were monitored. Disappearance of some of the 18 antibiotics was monitored by HPLC (high performance liquid chromatography) analysis. The antibiotics were used in two concentrations: (a) according to OECD 301 D in the mg/l-range and (b) on the basis of calculated concentrations in the influent of STPs in the microg/l-range. None of the 18 antibiotics were readily biodegradable. The HPLC analysis showed that some substances were partially or even completely disappeared by a non-biotic mechanism. In the case of some antibiotics, partial biological removal took place in test vessels containing readily biodegradable sodium acetate and the test compound. However, in the toxicity control, toxicity had not been eliminated.     

Acidic pharmaceuticals in domestic wastewater and receiving water from hyper-urbanization city of China (Shanghai): environmental release and ecological risk

The occurrence, behavior, and release of five acidic pharmaceuticals, including ibuprofen (IBP), naproxen (NPX), ketoprofen (KEP), diclofenac (DFC), and clofibric acid (CA), have been investigated along the different units in a tertiary-level domestic wastewater treatment plant (WWTP) in hyper-urbanization city of China (Shanghai). IBP was the most abundant chemicals among the measured in raw wastewater. The loads of the acidic pharmaceuticals in the WWTP influent ranged from 7.5 to 414 mg/day/1,000 inh, which were lower than those reported in the developed countries suggesting a less per capita consumption of pharmaceuticals in Shanghai. IBP obtained by highest removal (87 %); NPX and KEP were also significantly removed (69–76 %). However, DFC and CA were only moderately removed by 37–53 %, respectively. Biodegradation seemed to play a key role in the elimination of the studied pharmaceuticals except for DFC and CA. An annual release of acidic pharmaceuticals was estimated at 1,499 and 61.7 kg/year through wastewater and sludge, respectively, from Shanghai. Highest pharmaceuticals concentrations were detected in the effluent discharge point of the WWTP, indicating that WWTP effluent is the main source of the acidic pharmaceuticals to its receiving river. Preliminary results indicated that only DFC in river had a high risk to aquatic organisms. Nevertheless, the joint toxicity effects of these chemicals are needed to further investigate.