BackgroundThe social and medical problems of drug abuse are a matter of increasing global concern. To tackle drug abuse in changing scenarios, international drug agencies need fresh methods to monitor trends and patterns of illicit drug consumption.ObjectiveWe tested a sewage epidemiology approach, using levels of excreted drug residues in wastewater, to monitor collective use of the major drugs of abuse in near real time.MethodsSelected drug target residues derived from use of cocaine, opiates, cannabis, and amphetamines were measured by mass spectrometry in wastewater collected at major sewage treatment plants in Milan (Italy), Lugano (Switzerland), and London (United Kingdom). The amounts of drug residues conveyed to the treatment plants, reflecting the amounts collectively excreted with urine, were used to estimate consumption of the active parent drugs.ResultsReproducible and characteristic profiles of illicit drug use were obtained in the three cities, thus for the first time quickly revealing changes in local consumption (e.g., cocaine consumption rose significantly on weekends in Milan). Profiles of local drug consumption based on waste-water measurements are in line with national annual prevalence estimates.ConclusionsPatterns and trends of drug abuse in local communities can be promptly monitored by this tool, a convenient new complement to more complex, lengthy survey methods. In principle, searching the sewage for excreted compounds relevant to public health issues appears to have the potential to become a convenient source of real-time epidemiologic information.

A listing of "priority pharmaceuticals" for human use in Italy resulted in the selection of 26 pharmaceuticals, belonging to 11 therapeutic classes. They were analyzed by liquid chromatography-tandem mass spectrometry, their occurrence was assessed in six sewage treatment plants (STPs), and the loads and the removal rates (RR) were studied. Total loads ranged from 1.5 to 4.5 g/day/1000 inhabitants in influents and 1.0 and 3.0 g/day/1000 inhabitants in effluents. Total RR in STPs were mostly lower than 40%. Pharmaceuticals could be divided into three groups according to their behavior in STPs: one group with RR higher in summer than in winter, one group with RR similar in summer and winter, and a last group not removed. Last, we studied the distribution and fate of residual pharmaceuticals in the surface waters receiving the effluents of the STPs and identified degradation and sorption as the major factors affecting attenuation. Ciprofloxacin, ofloxacin, sulfamethoxazole (antibiotics), atenolol (cardiovascular drug), ibuprofen (antiinflammatory), furosemide, hydrochlorothiazide (diuretics), ranitidine (gastrointestinal drug), and bezafibrate (lipid regulator) were the most abundant residual drugs, thus those of environmental concern.

BackgroundCocaine use seems to be increasing in some urban areas worldwide, but it is not straightforward to determine the real extent of this phenomenon. Trends in drug abuse are currently estimated indirectly, mainly by large-scale social, medical, and crime statistics that may be biased or too generic. We thus tested a more direct approach based on 'field' evidence of cocaine use by the general population.MethodsCocaine and its main urinary metabolite (benzoylecgonine, BE) were measured by mass spectrometry in water samples collected from the River Po and urban waste water treatment plants of medium-size Italian cities. Drug concentration, water flow rate, and population at each site were used to estimate local cocaine consumption.ResultsWe showed that cocaine and BE are present, and measurable, in surface waters of populated areas. The largest Italian river, the Po, with a five-million people catchment basin, steadily carried the equivalent of about 4 kg cocaine per day. This would imply an average daily use of at least 27 ± 5 doses (100 mg each) for every 1000 young adults, an estimate that greatly exceeds official national figures. Data from waste water treatment plants serving medium-size Italian cities were consistent with this figure.ConclusionThis paper shows for the first time that an illicit drug, cocaine, is present in the aquatic environment, namely untreated urban waste water and a major river. We used environmental cocaine levels for estimating collective consumption of the drug, an approach with the unique potential ability to monitor local drug abuse trends in real time, while preserving the anonymity of individuals. The method tested here – in principle extendable to other drugs of abuse – might be further refined to become a standardized, objective tool for monitoring drug abuse.

Residues of illicit drugs and their metabolites that are excreted by humans may flow into and through wastewater treatment plants. The aim of this study was to develop a method for the determination of cocaine, amphetamines, morphine, cannabinoids, methadone, and some of their metabolites in wastewater. Composite 24-h samples from urban treatment plants were enriched with deuterated internal standards before solid-phase extraction. High-pressure liquid chromatography tandem mass spectrometry with multiple reaction monitoring was used for quantitation. Recoveries were generally higher than 80%, and limits of quantifications were in the low nanograms-per-liter range for untreated and treated wastewater. The overall variability of the method was lower than 10% for untreated and 5% for treated wastewater. The method was applied to wastewater samples coming from two treatment plants in Italy and Switzerland. Quantification ranges were found to be 0.2-1 microg/L for cocaine and its metabolite benzoylecgonine, 80-200 ng/L for morphine, 10 ng/L for 6-acetylmorphine, 60-90 ng/L for 11-nor-9-carboxy-Delta9-tetrahydrocannabinol, 10-90 ng/L for methadone and its main metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, and lower than 20 ng/L for amphetamines. As previously reported for cocaine, this method could be useful to estimate and monitor drug consumption in the population in real time, helping social scientists and authorities to combat drug abuse.

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A survey was done in the river Po (Italy) to check for therapeutic drugs in the environment. A number of pharmaceuticals were selected for analysis on the basis of high consumption and excretion as parent compound in humans. Eight sampling stations along the rivers Po and Lambro made it possible to plot the patterns of contamination in a highly populated region with a large number of animal farms. Atenolol, lincomycin, erythromycin, clarithromycin, bezafibrate, and furosemide were present at all the sampling sites, and other drugs were found only in some. Concentrations ranged from 0.1 to 250 ng/L, and several drugs exceeded the trigger value (10 ng/L) suggested by recent documents from the European Agency for the Evaluation of Medicinal Products (EMEA), assessing environmental risks for these chemicals. The patterns of contamination showed differences among sub-basins which correlated with the presence of large human settlements and/ or animal farms. The ratio of measured to predicted concentrations (MEC/PEC) allowed a gross division of the drugs into two groups. The first consisted of pharmaceuticals with a MEC/PEC in the range 0.01-0.3, where the ratio is probably determined by the environmental behavior and the extent of degradation of the molecule. The other group consisted of pharmaceuticals found at concentrations higher than those predicted (MEC/PEC > 1). In this group, which consists of drugs sold without prescription or for veterinary use, market justifications (sales load uncertainty) have more role than chemical properties and environmental fate in explaining the differences between measured and predicted environmental concentrations.

The potential risk associated with the presence of low levels of pharmaceuticals in aquatic environments is currently under debate. In this study we investigated the effects of 13 drugs merged to mimic both the association and low concentration (ng/L) profiles detected in the environment. The mixture comprised atenolol, bezafibrate, carbamazepine, cyclophosphamide, ciprofloxacin, furosemide, hydrochlorothiazide, ibuprofen, lincomycin, ofloxacin, ranitidine, salbutamol, and sulfamethoxazole. At environmental exposure levels, the drug mix inhibited the growth of human embryonic cells HEK293, with the highest effect observed as a 30% decrease in cell proliferation compared to controls. Pharmaceuticals activated stress-response signaling protein kinases (ERK1/2), and induced overexpression of glutathione-S-transferase P1 gene. No evidence was found for apoptosis or necrosis in HEK293 cells, although morphological changes were observed. The drug mixture effectively stimulated the expression of cell-cycle progression-mediating genes p16 and p21, with a slight accumulation of cells in the G2/M phase of the cell-cycle. Our results suggest that a mixture of drugs at ng/L levels can inhibit cells proliferation by affecting their physiology and morphology. This also suggests that water-borne pharmaceuticals can be potential effectors on aquatic life.

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