RESUMO
The consumption patterns of five categories of psychoactive substances (PS), including "conventional" illicit drugs, new psychoactive substances (NPS), therapeutic opioids, alcohol and nicotine, were studied in the city of Split, Croatia, using wastewater-based epidemiology (WBE), with an emphasis on the impact of a large electronic music festival. The study involved the analysis of 57 urinary biomarkers of PS in raw municipal wastewater samples collected in three characteristic periods, including the festival week in the peak-tourist season (July) and reference weeks in the peak-tourist season (August) and the off-tourist season (November). Such a large number of biomarkers allowed the recognition of distinct patterns of PS use associated with the festival, but also revealed some subtle differences between summer and autumn seasons. The festival week was characterized by markedly increased use of illicit stimulants (MDMA: 30-fold increase; cocaine and amphetamine: 1.7-fold increase) and alcohol (1.7-fold increase), while consumption of other common illicit drugs (cannabis and heroin), major therapeutic opioids (morphine, codeine and tramadol) and nicotine remained rather constant. Interestingly, NPS and methamphetamine clearly contributed to the festival PS signature in wastewater, but their prevalence was rather low compared to that of common illicit drugs. Estimates of cocaine and cannabis use were largely consistent with prevalence data from national surveys, whereas differences were found for typical amphetamine-type recreational drugs, particularly MDMA, and for heroin. The WBE data suggest that the largest proportion of morphine came from heroin consumption and that the percentage of heroin users seeking treatment in Split is probably rather low. The prevalence of smoking calculated in this study (30.6 %) was consistent with national survey data for 2015 (27.5-31.5 %), while the average alcohol consumption per capita >15 years (5.2 L) was lower than sales statistics suggest (8.9 L).
Assuntos
Cocaína , Drogas Ilícitas , Música , N-Metil-3,4-Metilenodioxianfetamina , Transtornos Relacionados ao Uso de Substâncias , Poluentes Químicos da Água , Humanos , Águas Residuárias , Nicotina/análise , Analgésicos Opioides/análise , Heroína/análise , Férias e Feriados , Drogas Ilícitas/análise , Anfetamina , Cocaína/análise , Etanol/análise , Detecção do Abuso de Substâncias , Poluentes Químicos da Água/análise , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
Wastewater-based epidemiology (WBE) can be a useful complementary approach to assess human exposure to potentially harmful chemicals, including those from personal care and household products. In this work, a fully automated multiresidue method, based on on-line solid-phase extraction liquid chromatography - tandem mass spectrometry, was developed for the determination of 27 biomarkers of human exposure to selected chemicals from personal care and household products, including parabens, UV filters, phthalates and alternative plasticizers, phosphorous flame retardants/plasticizers (PFRs), and bisphenols. These biomarkers include both the parent compounds and their human metabolites. In addition, two oxidative stress biomarkers, 8-epi-prostaglandin F2α and 4-hydroxy nonenal mercapturic acid, were also considered in the study. The method was carefully optimized to tackle the challenges of analyzing compounds with different physico-chemical properties in a highly complex raw wastewater matrix, while model experiments were performed to investigate filtration losses and analyte stability. The applicability of the developed method was tested by analyzing raw wastewater from four European cities: Antwerp, Brussels (Belgium), Girona (Spain), and Zagreb (Croatia). Twenty-one biomarkers (10 parent compounds and 11 metabolites) were detected in all analyzed wastewater samples. The parent compounds with the highest mass loads were PFRs, parabens, and bisphenol S, while phthalate monoesters were the most prominent metabolites. The mass loads of most compounds were quite similar across cities, but geographic differences were observed for some biomarkers, such as metabolites of phthalates and alternative plasticizers. Exposure was then assessed for seven substances for which quantitative urinary excretion data are known. Our results indicate that safe reference values were exceeded for several contaminants, including butylated phthalates, bisphenol A, and tris(2-butoxyethyl) phosphate, particularly for toddlers. With this relatively simple method, which requires less sample manipulation, it is possible to promptly identify and monitor exposure to harmful chemicals at the population level using the WBE approach.
Assuntos
Plastificantes , Águas Residuárias , Biomarcadores/urina , Cromatografia Líquida , Produtos Domésticos/análise , Humanos , Parabenos/análise , Plastificantes/análise , Extração em Fase Sólida , Espectrometria de Massas em Tandem , Águas Residuárias/químicaRESUMO
Macrolide antibiotics azithromycin (AZI), erythromycin (ERY) and clarithromycin (CLA) have been recently included in the EU Watch List of contaminants of emerging concern in the aquatic environment. However, their comprehensive assessment in different environmental compartments, by including synthesis intermediates, by-products and transformation products, is still missing. In this work, a novel method, based on pressurized liquid extraction and liquid chromatography-tandem mass spectrometry, was developed and validated for the determination of such an extended range of macrolide residues in sediment and soil samples at low ng/g levels. The method was applied to determine distribution of 13 macrolides in surface and alluvial aquifer sediments collected in a small stream with a history of chronic exposure to wastewater discharges from AZI production. The total concentrations of the target macrolide compounds in surface sediments were up to 29 µg/g and the most prominent individual macrolides were parent AZI, its synthesis intermediate N-demethyl AZI and transformation products decladinosyl AZI and N'-demethyl AZI. Some ERY-related compounds, originating from AZI synthesis, were also frequently detected, though at lower concentration levels (up to 0.31 ng/g in total). The distribution of macrolide residues in surface sediments indicated their active longitudinal transport by resuspension and redeposition of the contaminated sediment particles. The vertical concentration profiles in stream sediments and the underlying alluvial aquifer revealed that macrolide residues reached deeper alluvial sediments (up to 5 m). Moreover, significant levels of macrolides were found in groundwater samples below the streambed, with the total concentrations reaching up to 1.7 µg/L. This study highlights the importance of comprehensive chemical characterization of the macrolide residues, which were shown to persist in surface and alluvial aquifer sediment more than ten years after their discharge into the aquatic environment.
RESUMO
Environmental discharges of very high (mg/L) antibiotic levels from pharmaceutical production contributed to the selection, spread and persistence of antibiotic resistance. However, the effects of less antibiotic-polluted effluents (µg/L) from drug-formulation on exposed aquatic microbial communities are still scarce. Here we analyzed formulation effluents and sediments from the receiving creek collected at the discharge site (DW0), upstream (UP) and 3000â¯m downstream of discharge (DW3000) during winter and summer season. Chemical analyses indicated the largest amounts of trimethoprim (up to 5.08â¯mg/kg) and azithromycin (up to 0.39â¯mg/kg) at DW0, but sulfonamides accumulated at DW3000 (total up to 1.17â¯mg/kg). Quantitative PCR revealed significantly increased relative abundance of various antibiotic resistance genes (ARGs) against ß-lactams, macrolides, sulfonamides, trimethoprim and tetracyclines in sediments from DW0, despite relatively high background levels of some ARGs already at UP site. However, only sulfonamide (sul2) and macrolide ARG subtypes (mphG and msrE) were still elevated at DW3000 compared to UP. Sequencing of 16S rRNA genes revealed pronounced changes in the sediment bacterial community composition from both DW sites compared to UP site, regardless of the season. Numerous taxa with increased relative abundance at DW0 decreased to background levels at DW3000, suggesting die-off or lack of transport of effluent-originating bacteria. In contrast, various taxa that were more abundant in sediments than in effluents increased in relative abundance at DW3000 but not at DW0, possibly due to selection imposed by high sulfonamide levels. Network analysis revealed strong correlation between some clinically relevant ARGs (e.g. blaGES, blaOXA, ermB, tet39, sul2) and taxa with elevated abundance at DW sites, and known to harbour opportunistic pathogens, such as Acinetobacter, Arcobacter, Aeromonas and Shewanella. Our results demonstrate the necessity for improved management of pharmaceutical and rural waste disposal for mitigating the increasing problems with antibiotic resistance.
Assuntos
Resistência Microbiana a Medicamentos , Genes Bacterianos , Antibacterianos , Bactérias , Sedimentos Geológicos , RNA Ribossômico 16S , Águas ResiduáriasRESUMO
Humans are nowadays exposed to numerous chemicals in our day-to-day life, including parabens, UV filters, phosphorous flame retardants/plasticizers, bisphenols, phthalates and alternative plasticizers, which can have different adverse effects to human health. Estimating human's exposure to these potentially harmful substances is, therefore, of paramount importance. Human biomonitoring (HBM) is the existing approach to assess exposure to environmental contaminants, which relies on the analysis of specific human biomarkers (parent compounds and/or their metabolic products) in biological matrices from individuals. The main drawback is its implementation, which involves complex cohort studies. A novel approach, wastewater-based epidemiology (WBE), involves estimating exposure from the analysis of biomarkers in sewage (a pooled urine and feces sample of an entire population). One of the key challenges of WBE is the selection of biomarkers which are specific to human metabolism, excreted in sufficient amounts, and stable in sewage. So far, literature data on potential biomarkers for estimating exposure to these chemicals are scattered over numerous pharmacokinetic and HBM studies. Hence, this review provides a list of potential biomarkers of exposure to more than 30 widely used chemicals and report on their urinary excretion rates. Furthermore, the potential and challenges of WBE in this particular field is discussed through the review of pioneer WBE studies, which for the first time explored applicability of this novel approach to assess human exposure to environmental contaminants. In the future, WBE could be potentially applied as an "early warning system", which could promptly identify communities with the highest exposure to environmental contaminants.
RESUMO
A one-year study on the occurrence and fate of macrolide antibiotics and their metabolites, synthesis byproducts, and transformation products (TPs) was performed in the wastewater treatment plant of the city of Zagreb (Croatia). The target compounds were found in all analyzed influent and effluent samples with the total concentrations of azithromycin-, clarithromycin-, and erythromycin-related compounds reaching up to 25, 12, and 0.25 µg/L, respectively. The most prominent individual constituents were the parent macrolides azithromycin and clarithromycin. However, a substantial contribution of their derivatives, formed by deglycolysation and microbial phosphorylation, was also detected. In addition, widespread presence of several linearized nontarget TPs was confirmed for the first time in real wastewater samples by suspect screening analysis. Complex characterization of macrolide-derived compounds enabled decoupling of industrial and therapeutic sources from the in situ transformations. Due to the high inputs and incomplete removal and/or formation of several TPs during the conventional wastewater treatment, the average mass load of azithromycin-related compounds in secondary effluents exceeded 3.0 g/day/1000 inhabitants. This is the first study to reveal the importance of metabolites, byproducts, and TPs for the overall mass balance of macrolide antibiotics in urban wastewater systems.
Assuntos
Águas Residuárias , Poluentes Químicos da Água , Antibacterianos , Macrolídeos , Eliminação de Resíduos LíquidosRESUMO
Effluents from antibiotic manufacturing may contain high concentrations of antibiotics, which are the main driving force behind the selection and spread of antibiotic resistance genes in the environment. However, our knowledge about the impact of such effluent discharges on the antibiotic resistome and bacterial communities is still limited. To gain insight into this impact, we collected effluents from an azithromycin-manufacturing industry discharge site as well as upstream and downstream sediments from the receiving Sava river during both winter and summer season. Chemical analyses of sediment and effluent samples indicated that the effluent discharge significantly increased the amount of macrolide antibiotics, heavy metals and nutrients in the receiving river sediments. Quantitative PCR revealed a significant increase of relative abundances of macrolide-resistance genes and class 1 integrons in effluent-impacted sediments. Amplicon sequencing of 16S rRNA genes showed spatial and seasonal bacterial community shifts in the receiving sediments. Redundancy analysis and Mantel test indicated that macrolides and copper together with nutrients significantly correlated with community shift close to the effluent discharge site. The number of taxa that were significantly increased in relative abundance at the discharge site decreased rapidly at the downstream sites, showing the resilience of the indigenous sediment bacterial community. Seasonal changes in the chemical properties of the sediment along with changes in effluent community composition could be responsible for sediment community shifts between winter and summer. Altogether, this study showed that the discharge of pharmaceutical effluents altered physicochemical characteristics and bacterial community of receiving river sediments, which contributed to the enrichment of macrolide-resistance genes and integrons.
Assuntos
Azitromicina , Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Rios/microbiologia , Poluição Química da Água/efeitos adversos , Resistência Microbiana a Medicamentos/genética , Monitoramento Ambiental , Genes Bacterianos , Sedimentos Geológicos/química , Integrons , Metais Pesados/análise , Microbiota/efeitos dos fármacos , RNA Ribossômico 16S/genética , Rios/química , Estações do Ano , Águas Residuárias/química , Microbiologia da ÁguaRESUMO
A comprehensive study aimed at monitoring of temporal variability of illicit drugs (heroin, cocaine, amphetamine, MDMA, methamphetamine and cannabis) and therapeutic opiate methadone in a large-sized European city using wastewater-based epidemiology (WBE) was conducted in the city of Zagreb, Croatia, during an 8-year period (2009-2016). The study addressed the impact of different sampling schemes on the assessment of temporal drug consumption patterns, in particular multiannual consumption trends and documented the possible errors associated with the one-week sampling scheme. The highest drug consumption prevalence was determined for cannabis (from 59⯱â¯18 to 156⯱â¯37 doses/day/1000 inhabitants 15-64â¯years), followed by heroin (from 11⯱â¯10 to 71⯱â¯19 doses/day/1000 inhabitants 15-64â¯years), cocaine (from 8.3⯱â¯0.9 to 23⯱â¯4.0 doses/day/1000 inhabitants 15-64â¯years) and amphetamine (from 1.3⯱â¯0.9 to 21⯱â¯6.1 doses/day/1000 inhabitants 15-64â¯years) whereas the consumption of MDMA was comparatively lower (from 0.18⯱â¯0.08 to 2.7 doses ±0.7 doses/day/1000 inhabitants 15-64â¯years). The drug consumption patterns were characterized by clearly enhanced weekend and Christmas season consumption of stimulating drugs (cocaine, MDMA and amphetamine) and somewhat lower summer consumption of almost all drugs. Pronounced multiannual consumption trends were determined for most of the illicit drugs. The investigated 8-year period was characterized by a marked increase of the consumption of pure cocaine (1.6-fold), THC (2.7-fold), amphetamine (16-fold) and MDMA (15-fold) and a concomitant decrease (2.3-fold) of the consumption of pure heroin. The heroin consumption decrease was associated with an increase of methadone consumption (1.4-fold), which can be linked to its use in the heroin substitution therapy. The estimated number of average methadone doses consumed in the city of Zagreb was in a good agreement with the prescription data on treated opioid addicts in Croatia.
Assuntos
Drogas Ilícitas/análise , Detecção do Abuso de Substâncias , Poluentes Químicos da Água/análise , Cidades , Croácia , Monitoramento Ambiental , Humanos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Águas Residuárias/químicaRESUMO
The biotransformation of three prominent macrolide antibiotics (azithromycin, clarithromycin and erythromycin) by an activated sludge culture, which was adapted to high concentrations of azithromycin (10â¯mg/L) was investigated. The study included determination of removal kinetics of the parent compounds, identification of their major biotransformation products (TPs) and assessment of ecotoxicological effects of biotransformation. The chemical analyses were performed by ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry, which enabled a tentative identification of TPs formed during the experiments. The ecotoxicological evaluation included two end-points, residual antibiotic activity and toxicity to freshwater algae. The enriched activated sludge culture was capable of degrading all studied macrolide compounds with high removal efficiencies (>99%) of the parent compounds at elevated concentrations (10â¯mg/L). The elimination of all three macrolide antibiotics was associated with the formation of different TPs, including several novel compounds previously unreported in the literature. Some of the TPs were rather abundant and contributed significantly to the overall mass balance at the end of the biodegradation experiments. Biodegradation of all investigated macrolides was associated with a pronounced reduction of the residual antibiotic activity and algal toxicity, indicating a rather positive ecotoxicological outcome of the biotransformation processes achieved by the enriched sludge culture.
Assuntos
Antibacterianos/metabolismo , Macrolídeos/metabolismo , Esgotos , Antibacterianos/toxicidade , Biotransformação , Clorófitas/efeitos dos fármacos , Clorófitas/crescimento & desenvolvimento , Ecotoxicologia , Cinética , Macrolídeos/toxicidadeRESUMO
Effluents from pharmaceutical industries are recognized as significant contributors to aquatic pollution with antibiotics. Although such pollution has been mostly reported in Asia, knowledge on industrial discharges in other regions of the world, including Europe, and on the effects associated with such exposures is still limited. Thus, we performed chemical, microbiological and ecotoxicological analyses of effluents from two Croatian pharmaceutical industries during four seasons. In treated effluents of the company synthesizing macrolide antibiotic azithromycin (AZI), the total concentration of AZI and two macrolide by-products from its synthesis was 1-3 orders of magnitude higher in winter and springtime (up to 10.5 mg/L) than during the other two seasons (up to 638 µg/L). Accordingly, the highest total concentrations (up to 30 µg/L) in the recipient river were measured in winter and spring. Effluents from second company formulating veterinary antibiotics contained fluoroquinolones, trimethoprim, sulfonamides and tetracyclines ranging from low µg/L to approx. 200 µg/L. Low concentrations of these antibiotics, from below the limit of quantification to approx. few µg/L, have also been measured in the recipient stream. High frequency of culturable bacteria resistant to AZI (up to 83%) or sulfamethazine (up to 90%) and oxytetracycline (up to 50%) were also found in studied effluents. Finally, we demonstrated that toxicity to algae and water fleas often exceeded the permitted values. Most highly contaminated effluents induced multiple abnormalities in zebrafish embryos. In conclusion, using a wide array of analyses we have demonstrated that discharges from pharmaceutical industries can pose a significant ecological and public health concern due to their toxicity to aquatic organisms and risks for promoting development and spread of antibiotic resistance.
Assuntos
Antibacterianos/análise , Antibacterianos/toxicidade , Indústria Farmacêutica , Poluentes Químicos da Água/análise , Animais , Organismos Aquáticos/efeitos dos fármacos , Cladocera/efeitos dos fármacos , Croácia , Daphnia/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Resistência Microbiana a Medicamentos , Ecotoxicologia/métodos , Embrião não Mamífero/efeitos dos fármacos , Meio Ambiente , Monitoramento Ambiental , Resíduos Industriais/análise , Rios/química , Estações do Ano , Drogas Veterinárias/análise , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologiaRESUMO
Wastewater-based epidemiology is a promising and complementary tool for estimating drug use by the general population, based on the quantitative analysis of specific human metabolites of illicit drugs in urban wastewater. Cannabis is the most commonly used illicit drug and of high interest for epidemiologists. However, the inclusion of its main human urinary metabolite 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in wastewater-based epidemiology has presented several challenges and concentrations seem to depend heavily on environmental factors, sample preparation and analyses, commonly resulting in an underestimation. The aim of the present study is to investigate, identify and diminish the source of bias when analysing THC-COOH in wastewater. Several experiments were performed to individually assess different aspects of THC-COOH determination in wastewater, such as the number of freeze-thaw cycles, filtration, sorption to different container materials and in-sample stability, and the most suitable order of preparatory steps. Results highlighted the filtration step and adjustment of the sample pH as the most critical parameters to take into account when analysing THC-COOH in wastewater. Furthermore, the order of these initial steps of the analytical procedure is crucial. Findings were translated into a recommended best-practice protocol and an inter-laboratory study was organized with eight laboratories that tested the performance of the proposed procedure. Results were found satisfactory with z-scores ≤ 2.
Assuntos
Cannabis , Dronabinol/análise , Drogas Ilícitas/análise , Águas Residuárias/análise , HumanosRESUMO
BACKGROUND: Analysis of student consumption of illicit drugs (ID) by school population surveys (SPS) provides information useful for prevention, but the results may be influenced by subjective factors. We explored wastewater (WW) analysis to improve the information. METHODS: We used WW analysis to measure ID consumption in eight secondary schools in Italy in 2010-13 (students aged 15-19). Samples were collected from the sewage pipes of the schools during lessons for one week each year. Samples were analysed by mass spectrometry to measure ID and consumption by students was compared to that of the general population. RESULTS: We found THCCOOH (human metabolite of THC) concentrations in 2010 indicating significant consumption of cannabis in all the schools and benzoylecgonine (human metabolite of cocaine) suggesting a limited consumption of cocaine in all but one school. Morphine was only found in traces, and amphetamine, methamphetamine, ecstasy, ketamine and mephedrone were not detectable. Repeated analysis showed cannabis stable until 2012 with increases in 2013, low cocaine and morphine levels, and none of the other ID. DISCUSSION: WW analysis suggested that students used amounts of cannabis comparable to the general population, with low, sporadic use of cocaine and opioids, but excluded the use of significant amounts of amphetamine, methamphetamine, ecstasy, ketamine and mephedrone. WW analysis was useful to confirm SPS figures and provides complementary findings for effective prevention strategies. This is the first time WW analysis has been used to investigate consumption of a large number of ID and new psychoactive substances (NPS) in schools.
Assuntos
Anfetamina/análise , Canabinoides/análise , Cocaína/análogos & derivados , Drogas Ilícitas/análise , Ketamina/análise , Metanfetamina/análogos & derivados , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Águas Residuárias/análise , Anfetamina/química , Canabinoides/química , Cannabis/efeitos dos fármacos , Cocaína/química , Humanos , Itália , Ketamina/química , Espectrometria de Massas , Metanfetamina/análise , Metanfetamina/química , N-Metil-3,4-Metilenodioxianfetamina/análiseRESUMO
Macrolide antibiotics are a prominent group of emerging contaminants frequently found in wastewater effluents and wastewater-impacted aquatic environments. In this work, a novel analytical method for simultaneous determination of parent macrolide antibiotics (azithromycin, erythromycin, clarithromycin and roxithromycin), along with their synthesis intermediates, byproducts, metabolites and transformation products in wastewater and surface water was developed and validated. Samples were enriched using solid-phase extraction on Oasis HLB cartridges and analyzed by reversed-phase liquid chromatography coupled to electrospray ionization tandem mass spectrometry. The target macrolide compounds were separated on an ACE C18 PFP column and detected using multiple reaction monitoring in positive ionization polarity. The optimized method, which included an additional extract clean-up on strong anion-exchange cartridges (SAX), resulted in high recoveries and accuracies, low matrix effects and improved chromatographic separation of the target compounds, even in highly complex matrices, such as raw wastewater. The developed method was applied to the analysis of macrolide compounds in wastewater and river water samples from Croatia. In addition to parent antibiotics, several previously unreported macrolide transformation products and/or synthesis intermediates were detected in municipal wastewater, some of them reaching µg/L levels. Moreover, extremely high concentrations of macrolides up to mg/L level were found in pharmaceutical industry effluents, indicating possible importance of this source to the total loads into ambient waters. The results revealed a significant contribution of synthesis intermediates and transformation products to the overall mass balance of macrolides in the aquatic environment.
Assuntos
Antibacterianos/química , Cromatografia Líquida/métodos , Água Doce/química , Macrolídeos/química , Espectrometria de Massas em Tandem/métodos , Águas Residuárias/química , Poluentes Químicos da Água/química , Antibacterianos/síntese química , Antibacterianos/isolamento & purificação , Macrolídeos/síntese química , Macrolídeos/isolamento & purificação , Extração em Fase Sólida , Espectrometria de Massas por Ionização por Electrospray/métodos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/síntese química , Poluentes Químicos da Água/isolamento & purificaçãoRESUMO
The information obtained from the chemical analysis of specific human excretion products (biomarkers) in urban wastewater can be used to estimate the exposure or consumption of the population under investigation to a defined substance. A proper biomarker can provide relevant information about lifestyle habits, health and wellbeing, but its selection is not an easy task as it should fulfil several specific requirements in order to be successfully employed. This paper aims to summarize the current knowledge related to the most relevant biomarkers used so far. In addition, some potential wastewater biomarkers that could be used for future applications were evaluated. For this purpose, representative chemical classes have been chosen and grouped in four main categories: (i) those that provide estimates of lifestyle factors and substance use, (ii) those used to estimate the exposure to toxicants present in the environment and food, (iii) those that have the potential to provide information about public health and illness and (iv) those used to estimate the population size. To facilitate the evaluation of the eligibility of a compound as a biomarker, information, when available, on stability in urine and wastewater and pharmacokinetic data (i.e. metabolism and urinary excretion profile) has been reviewed. Finally, several needs and recommendations for future research are proposed.
Assuntos
Biomarcadores/análise , Poluentes Ambientais/análise , Preparações Farmacêuticas/análise , Densidade Demográfica , Saúde Pública , Águas Residuárias/análise , Humanos , Estilo de VidaRESUMO
A comprehensive study of spatial and temporal consumption patterns of the selected illicit drugs (heroin, cocaine, amphetamine, MDMA, methamphetamine, cannabis) and therapeutic opioids (codeine, methadone) has been performed in six Croatian cities by applying wastewater-based epidemiology. The investigated cities (Bjelovar, Vinkovci, Varazdin, Karlovac, Zadar and Zagreb) varied widely in the population size (27,000-688,000 inhabitants) as well as in the number of registered drug consumers included in compulsory and voluntary medical treatment and rehabilitation programs (30-513 persons/100,000 inhabitants of age 15-64). The most consumed illicit drugs were cannabis (10-70doses/day/1000 inhabitants), heroin (<0.2-10doses/day/1000 inhabitants) and cocaine (0.2-8.7doses/day/1000 inhabitants), while the consumption of amphetamine-type drugs was much lower (<0.01-4.4doses/day/1000 inhabitants). Enhanced consumption of illegal drugs was generally associated with larger urban centers (Zagreb and Zadar) however comparatively high consumption rate of cocaine, MDMA and methadone was determined in some smaller cities as well. The overall average dose number of 3 major illegal stimulants (cocaine, MDMA, amphetamine) was rather similar to the number of corresponding heroin doses, which is in disagreement with a comparatively much higher proportion of heroin users in the total number of registered drug users in Croatia. Furthermore, the illicit drug consumption pattern in the large continental city (Zagreb) was characterized by a significant enhancement of the consumption of all stimulants during the weekend, which could not be confirmed neither for the coastal city of Zadar nor for the remaining small continental cities. On the other hand, the city of Zadar exhibited a significant increase of stimulant drug usage during summer vacation period, as a result of pronounced seasonal changes of the population composition and lifestyle in coastal tourist centers. The obtained results represent a valuable complementary data source for the optimisation and implementation of strategies to combat drug abuse in Croatia.
Assuntos
Analgésicos Opioides/análise , Monitoramento Ambiental , Drogas Ilícitas/análise , Águas Residuárias/análise , Poluentes Químicos da Água/análise , Cidades , Croácia , Humanos , Estações do Ano , Detecção do Abuso de Substâncias , Fatores de TempoRESUMO
BACKGROUND: Monitoring consumption by population surveys (PS) is an important way to challenge the spread of illicit drugs (ID). To improve the information, we explored a complementary method, particularly wastewater analysis (WWA). METHODS: We estimated the prevalence of use by PS, and the consumption by WWA, of cocaine, opioids, cannabis, methamphetamine and MDMA (ecstasy) from 2010 to 2014 in Italy and compared the results. RESULTS: According to PS, cannabis and cocaine were the ID most used in Italy (last month prevalence 3.0% and 0.43% respectively in 2010) followed by opioids (0.17%) and amphetamines (0.14%). WWA gave similar findings, with cannabis consumption (4.35 g THC/day/1000 inhabitants) exceeding cocaine (0.78 g), heroin (0.092 g), methamphetamine and MDMA (0.103 g). The time trend investigated by PS showed significant decreases for all ID from 2010 to 2012. WWA also indicated a reduction of consumption for methamphetamine (p<0.0001) and heroin (p<0.01). Both methods showed an increase for cannabis in 2014 (p<0.001) with the other ID unchanged. Spatial investigations by WWA showed that cannabis and cocaine were consumed significantly more in central Italy than in the north and south. PS indicated the same but only for cannabis. WWA was helpful to study weekly patterns of consumption, showing increases in cocaine and MDMA at weekends. CONCLUSIONS: PS and WWA were confirmed as complementary methods and when used together improved the information on ID use in Italy. We suggest that the combined use of the two approaches can give better information on ID use in the population.
Assuntos
Uso de Medicamentos/estatística & dados numéricos , Drogas Ilícitas/análise , Detecção do Abuso de Substâncias/métodos , Águas Residuárias/química , Poluentes Químicos da Água/análise , Uso de Medicamentos/tendências , Humanos , Itália , Inquéritos e QuestionáriosRESUMO
Besides the common illicit drugs, such as cocaine, heroin, and marijuana, there is a growing concern about the use of modern "designer drugs" that have emerged in large numbers over the past few years. In this work, a sensitive and selective method for simultaneous determination of 25 synthetic amphetamine-like psychoactive compounds, including amphetamine, sympathomimetic substituted amphetamines, synthetic cathinones and ketamine, in raw wastewater (RW), secondary effluent (SE) and river water was developed. Samples were enriched by solid-phase extraction (SPE) on mixed-mode reversed-phase/strong cation-exchange sorbent (Oasis MCX) and analysed by reversed-phase liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (LC-MS/MS). The target compounds were separated on a Synergi Polar column and detected using multiple reaction monitoring (MRM) in positive ionisation mode. Accurate quantification was achieved by using several deuterated analogues as surrogate standards. Careful optimisation and validation of the procedure resulted in a reliable determination of all target analytes in low ng/L range for all matrices, which makes the method suitable for the application in wastewater-based epidemiology. The method was applied for assessment of selected compounds in municipal wastewater and river water from Croatia. It was shown that most of the wastewater samples contained detectable levels of the well-known synthetic illicit drugs, amphetamine and 3,4-methylenedioxy-methamphetamine (MDMA) (concentrations up to 545ng/L and 55ng/L in RW, respectively), as well as ephedrine (up to 108ng/L) and pseudoephedrine (up to 698ng/L), which are used as ingredients of popular over-the counter cough and cold medications. Other target amphetamine-like psychoactive substances, recently reported for their potential abuse, were detected only occasionally and in low concentrations (<10ng/L).
Assuntos
Anfetaminas/análise , Estimulantes do Sistema Nervoso Central/análise , Rios/química , Águas Residuárias/química , Poluentes Químicos da Água/análise , Cromatografia de Fase Reversa , Drogas Ilícitas/análise , Extração em Fase Sólida , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodosRESUMO
Wastewater analysis was applied in a four-year monitoring study to assess temporal and spatial patterns of ketamine and mephedrone use in the general population in Italy. Composite raw wastewater samples were collected from sewage treatment plants (STPs) in 17 cities. Target analytes were measured using a validated method based on solid phase extraction and liquid chromatography coupled to tandem mass spectrometry analysis. Mass loads were use to assess ketamine and mephedrone use and were normalized to the population served by the plants. Ketamine was detected in wastewater in all except one (Palermo) of the cities investigated, while mephedrone was detected only in Bologna and Florence. Ketamine mass loads progressively increased from 2010 to 2013, and in Milan rose from 1 to 1.5 g/day in 2008-2010 to 3.4-3.6 g/day in 2013-2014. Mass loads were higher in north and central Italy than in the south, and in larger rather than small cities. Wastewater analysis was suitable to provide objective and up-to-date information on the use of ketamine in Italy, to identify ketamine spatial and temporal changes, and to confirm the low use of mephedrone. These results can complement information from population surveys which often provide only scant and incomplete figures for these substances.
Assuntos
Monitoramento Ambiental , Drogas Ilícitas/análise , Ketamina/análise , Metanfetamina/análogos & derivados , Águas Residuárias/química , Poluentes Químicos da Água/análise , Cromatografia Líquida , Cidades , Itália , Metanfetamina/análise , Esgotos/química , Espectrometria de Massas em Tandem , Fatores de Tempo , Purificação da ÁguaRESUMO
The use of caffeine, nicotine and some major metabolites was investigated by wastewater analysis in 13 sewage treatment plants (STPs) across Italy, and their suitability was tested as qualitative and quantitative biomarkers for assessing population size and dynamics. A specific analytical method based on mass spectrometry was developed and validated in raw urban wastewater, and included two caffeine metabolites, 1-methylxanthine and 7-methylxanthine, never reported in wastewater before. All these compounds were found widely at the µg/L level. Mass loads, calculated by multiplying concentrations by the wastewater daily flow rate and normalized to the population served by each plant, were used to compare the profiles from different cities. Some regional differences were observed in the mass loads, especially for nicotine metabolites, which were significantly higher in the south than in the center and north of Italy, reflecting smoking prevalences from population surveys. There were no significant weekly trends, although the mean mass loads of caffeine and its metabolites were slightly lower during the weekend. Most caffeine and nicotine metabolites fulfilled the requirements for an ideal biomarker for the assessment of population size, i.e. being easily detectable in wastewater, stable in sewage and during sampling, and reflecting human metabolism. Nicotine metabolites were tested as quantitative biomarkers to estimate population size and the results agreed well with census data. Caffeine and its metabolites were confirmed as good qualitative biomarkers, but additional information is needed on the caffeine metabolism in relation to the multiple sources of its main metabolites. This exploratory study opens the way to the routine use of nicotine metabolites for estimating population size and dynamics.