Acta Poloniae Pharmaceutica ñ Drug Research, Vol. 76 No. 1 pp. 137ñ145, 2019 ISSN 0001-6837 DOI: 10.32383/appdr/94615 Polish Pharmaceutical Society

COCAINE CONSUMPTION IN THE CITY OF (SOUTHEAST OF ) ESTIMATED BY WASTEWATER ANALYSIS: APPLYING AN ACCURATE AND VALID TOOL TO OBTAIN OBJECTIVE DATA FOR DRUG ABUSE

LUCÕA FERN¡NDEZ-L”PEZ2, JAVIER NAVARRO-ZARAGOZA1*, FRANCISCO CARAVACA3, MARÕA FALC”N2 and AURELIO LUNA2

1Department of Pharmacology, University of Murcia, Spain 2Health and Social Sciences Department, University of Murcia, Spain 3Department of Social Work and Social Services, University Pablo de Olavide, Spain

Abstract: Cocaine consumption is one of the most relevant public health issues in America and Europe. There are different methods to estimate cocaine consumption, with different levels of accuracy. Although surveys are one of the most employed methods, it usually underestimates cocaine consumption. Recent studies have vali- dated the use of wastewater analysis as the method that would provide more accurate results, as it is based on the analysis of residues of illicit drugs and their metabolites that are excreted by human flow through waste- water treatment plants. This study aims to estimate cocaine consumption in the southeast of Spain by waste- water analysis. Samples were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC- MS/MS). According to this analysis, cocaine consumption has been estimated at 410.6 milligrams per day and per 1000 inhabitants, a higher result than that obtained at other European cities of similar size. Highest con- sumption occurs during the weekend, which is consistent with cocaine being categorized as a recreational drug. The results of this analysis show that cocaine use is increasing public health and economic problem. Finally, wastewater analysis offers different options to estimate its use in this region of Spain.

Keywords: wastewater, cocaine, mass spectrometry, drug consumption, benzoylecgonine, cocaethylene

Abbreviations (in alphabetical order):BOD: Biochemical Oxygen Demand, DPNSD: Government Delegation for the National Plan on Drug, EMCDDA: European Monitoring Centre for Drugs and Drug Addiction, ED: Emergency Department, EDADES: Household Survey on Alcohol and Drugs in Spain, FWHM: Full Width Half Maximum, GC/MS: Gas Chromatography-Mass Spectrometry, LC/MS: Liquid Chromatography-Mass Spectrometry, LOQ: Limit of Quantification, Q: Flow rate, RSD: Relative Standard Deviation, S/N: Signal-to- noise, SRM: Selective Reaction Monitoring, UNODC: United Nations Office on Drugs and Crime, UPLC- qTOF-MS/MS: Ultra-performance liquid chromatography quadrupole time of flight mass spectrometry

The illicit drugs consumption is increasing consumed cocaine so in the present year. According worldwide, mainly in America and Europe, which to previous studies, United Kingdom is the country leads to significant health and social behavior issues with the highest number of cocaine-related emer- that affect 27 million users (1-2). Consumption of gency episodes, followed by Spain (7). Both coun- heroin, cocaine and other drugs causes around 0.2 tries share a high consumption rate among young million deaths per year (183.000 drug-related deaths adults (aged 15ñ34) (5, 8, 9). were reported in 2012 (3)). Cocaine consumption in Spain is a critical Although cocaine, one of the most potent and issue. According to different surveys (10), the num- addictive illicit drugs, has been consumed for over a ber of adult population that have consumed cocaine century, its consumption seems to be increasing (4- at least once in their life has constantly increased 6). Cocaine is now the most commonly consumed since 1995 (11). Cocaine is currently the drug that illicit stimulant drug in Europe (4, 6). More than generates more visits (45.1%) to the Emergency 14.5 million Europeans have consumed cocaine at Department (ED) (5). Moreover, although mortality least once, and it has been estimated that 3.5 have after psychoactive substances use and abuse has

* Corresponding author: e-mail: [email protected]

137 138 LUCÕA FERN¡NDEZ-L”PEZ et al. decreased in Spain, the proportion of deaths where separation and determination using liquid (LC) or cocaine or its metabolites are involved continues gas chromatography (GC), coupled with mass spec- increasing (11). trometry (LC-MS or GC-MS). Gas chromatography- For many years, surveys have been the only mass spectrometry (GC-MS) and liquid chromato- affordable analytic method to measure drug con- graphy-mass spectrometry (LC-MS) are the tech- sumption. This system has different inconveniences, niques of choice for quantitative analysis. To have a including underestimation of consumption (12). The tandem mass offers better results than single-quadru- treatment of the sample let to obtain acceptable pole instruments, in terms of sensitivity and selecti- results for some drugs of abuse, but in contrast, vity. In contrast, LCñMS/MS has been the technique these surveys do not permit to obtain trustful results most referenced for polar and semi-polar organic for illicit drugs with less consumption, such as compounds analysis until currently (24). cocaine. One reason is statistical, another important The selection of appropriate DTRs is also reason is the fear of some minors to answer this kind essential to obtain reliable estimates of drug con- of surveys, although are anonymous (12). Another sumption. For this reason, the new good practices analytic method, wastewater-based drug epidemiol- protocol for WBE studies specifies that the sub- ogy (WBDE), has been increasingly employed as an stances should fulfill the following requirements: 1) alternative approach to socio-epidemiological sur- being excreted in consistent amounts in urine; 2) veys. This method consists analyzing drugs and being detectable in urban wastewater; 3) being sta- their metabolites or drug biomarkers in wastewater ble in wastewater and 4) have human excretion as samples from a target community (13). their unique source (25). Different methods have been developed in Since the proposal of this method, several stud- order to diagnose substances consumption by ies have been carried out in different countries (26- WBDE. Solid phase and headspace solid-phase 27). However, in Spain it has only been developed methods allow extracting residues and metabolites in cities of other regions (Santiago, Barcelona, of illicit drugs from hair and biological fluids like CastellÛn, Valencia) and one town from Murcia urine, sweat, blood or saliva. However, previous (Molina de Segura) but it has not become the pre- analyses of biological fluids have allowed to meas- ferred method to measure drug consumption, uring drug consumption by individuals, not by a although as said above, cocaine is a predominant community (1, 14-15). Residues of illicit drugs that drug of abuse very difficult to measure. Surveys are excreted by humans flow into and through suggest that the southeast of Spain is one of the wastewater treatment plants. These residues can regions where drugs consumption is higher. For produce a serious potential effect on humans, being these reasons, the aim of this study is to determine persistent (such as cocaine and its metabolite ben- the concentrations of cocaine and its metabolites zoylecgonine) in the environment (16). The metabo- in samples of wastewater from a water treatment lites maintain the same action of the original com- plant in the city of Murcia, in the Region of Mur- pound, thus generating toxicological effects on non- cia, Spain, in order to back-calculate cocaine con- target microorganisms (17). sumption. The proposed analysis of illicit drugs in waste- water is a reliable source of data to estimate sub- EXPERIMENTAL stances consumption in the population (18-19). This idea was proposed by Daughton in 2001 and applied Materials and chemicals by him and Zuccato (4, 20-22). Daughton hypothe- Cocaethylene-d3 and benzoylecgonine-d3 were sized that in a similar manner to medicinal com- purchased from Sigma-Aldrich (Steinheim, Germa- pounds, residues of illicit drugs may also be detected ny) as 0.1 mg/mL solutions in acetonitrile or in the aquatic environment as a result of human use. methanol. Diluted standard solutions were prepared As a consequence, it is possible to determine the in methanol HPLC (Sigma-Aldrich) until 10 µg/mL amount of drug used by a population by measuring as required. Ultrapure water was obtained from a the concentration of drugs residues in wastewater (1, Milli-Q Gradient A-10 system (Millipore, Bedford, 23). There are different procedures used to perform Massachusetts, USA). Ammonium acetate, acetic the determination of organic compounds in aquatic acid, formic acid and tetrabutylammonium bromide environmental matrices, i.e. solid-phase extraction (TBA, 99% purity) were purchased also at Sigma- (SPE), solid-phase microextraction (SPME), stir bar Aldrich. Cartridges (6-mL disposable Oasis MCX) sorptive extraction (SBSE) or liquid-liquid extrac- for solid-phase extraction (SPE) were acquired from tion (LLE). Besides, they are remarkable methods of Waters (Milford, Massachusetts, USA). Cocaine consumption in the city of Murcia (southeast of Spain) estimated by... 139

Wastewater sampling ESI interface operating in positive ion mode. The Raw influent wastewater was collected at the UPLC separation was performed using an Acquity inlet (before the primary clarifier) of the main UPLC BEH C18 1.7 µm particle size analytical col- wastewater treatment plant located in the province umn 50 mm ◊ 2.1 mm (Waters) at a flow rate of 0.3 of Murcia. The flow rate of this plant is around mL/min. Ther acquisition was performed in 108.000 m3/day and it covers 445.000 inhabitants. Selected Reaction Monitoring (SRM) mode. The

We decided to collect wastewater samples from the mobile phases used were A= H2O with 0.01% central area of the city, which consists of a popula- HCOOH and B = MeOH. The percentage of organ- tion of approximately 170.000 inhabitants and it ic modifier (B) was changed linearly as follows: 0 comprises a 70% of total flow rate according to data min, 10%; 14 min, 90%; 7 min, 90%; 9.0 min, 90%; from the wastewater treatment plant (Table 1). 9.01 min, 10%. Nitrogen (from a nitrogen generator) Samples of 250 mL were collected by auto- was used as the drying gas and nebulizing gas. The matic sampling devices every hour during 6 consec- gas flow was set at 320 L/h. TOF-MS resolution was utive days (24 samples/day). Water samples were approximately 45.000 at full width half maximum stored in dark bottles at -20OC until analysis. (FWHM) in V-mode and 17.500 FWHM in W mode, at m/z 556.2771. MS data were acquired over Sample preparation and analysis an m/z range of 50ñ1200. The microchannel plate Following the collection, water samples were detector potential was set to 1750 V. A capillary vacuum-filtered on a glass microfiber filter GF/A voltage of 4.5 kV and a cone voltage of 25 V were 1.6 µm (Whatman, UK) and then through 0.45 µm used. The interface temperature was set to 350OC nitrocellulose filters (Millipore, Bedford, Massachu- and the source temperature to 120OC. The column setts, USA) before extraction. Solid-phase extrac- temperature was set to 40OC. Calibrations were con- tion was performed as described below using 6-mL ducted from m/z 50 to 1200 with a 1 : 1 mixture of Oasis MCX cartridges. They were conditioned by 0.01 M NaOH : 5% HCOOH diluted (1 : 5) with iso- washing with 6 mL of methanol, 3 mL of Milli-Q propanol: water (1 : 1), at a flow rate of 180 µL/h. water, and 3 mL of acidified water (pH 2). Then 60 MS data were acquired in centroid mode and were mL-aliquots from wastewater samples were adjust- processed by the Data Analysis application manager ed to pH 2.0 with formic acid. Samples were loaded (within Compass 1.7; Bruker Corporation). LC onto the cartridges by gravity, washed with 5 mL of retention time was compared to the specified in the 2% ammonia in water and then dried for 5 min. standards, considering a deviation of 2.5%, in order Target substances were eluted using 8 mL of a 2% to confirm the metabolites detected by mass spec- ammonia solution in methanol. The obtained solu- trometry. tion was evaporated to dryness at 35OC under a In order to assure the quality of analytical stream of nitrogen. methods and to ensure the reliability of the results Immediately, dried samples were dissolved in (28-29), our parameters were defined. The limit of 1 mL of 10% methanol in water. Analyses were per- detection (LOD), which is the lowest concentration formed by injecting 25 µL of the final extract into that the method can differentiate from background the UPLC-qTOF-MS/MS system. A Waters Acquity results, was calculated for a signal-to-noise (S/N) of UPLC system (Waters, Milford, MA, USA) was three from the chromatograms spiked at the lowest interfaced to quadrupole-high resolutionñTOF mass analyte concentration tested. The limit of quantifica- spectrometer (HR-QTOF maXis impact, Bruker, tion (LOQ) was calculated as the lowest concentra- Bremen, Germany), using an orthogonal Z-spray- tion level for which this method was completely val-

Table 1. Total flow rate and flow rate target (70% of total flow rate) of each day. Day Flow rate (Q) (m3/day) Flow rate target (70%Q) (m3/day) Friday 113.552 79.486 Saturday 104.206 72.944 Sunday 100.947 70.663 Monday 102.506 71.754 Tuesday 108.461 75.922 Wednesday 114.250 79.975 140 LUCÕA FERN¡NDEZ-L”PEZ et al. idated by using spiked samples with an adequate cator of consumption (22). Regarding cocaine, its recovery (between 70 and 120%). Confirmation of main excretion product is benzoylecgonine, and these data was made through highly selective importantly, 45% of consumed cocaine is excreted by Multiple Reaction Monitoring (MRM). Instrumental this manner. The ratio molar mass cocaine/ben- detection and quantification limits for Cocaethylene zoylecgonine is 1.05 and the correction factor is 2.33. were 2-5 ng/L and ~14 ng/L respectively and about Benzoylecgonine 1-3 ng/L and ~12 ng/L. The lin- Cocaine and ethanol co-consumption earity of the method was analyzed by studying stan- We used the ratio cocaethylene/benzoylecgo- dard solutions in triplicate at six different concentra- nine to calculate directly the amount of cocaine con- tions, ranging from 0.5 µg/L to 25 µg/L for cocaine sumed together with alcohol. and its metabolites. Satisfactory linearity was set when the correlation coefficient (R) was greater than Statistical analysis 0.99, according to analyte/internal standard peak Data are expressed as mean ± SEM. Statistical areas size. Other different validation parameters analysis was determined by a two-way analysis of were measured as accuracy (which was calculated variance (ANOVA). The Newman-Keuls was used by means of recovery experiments) and of course, as a post hoc test whenever a significant result was precision (quantified as repeatability in terms of revealed by an analysis of variance (ANOVA). Relative Standard Deviation (RSD)) = 20%. Both Differences with a p < 0.05 were considered signif- were analyzed by injecting different water samples icant. spiked at different concentration levels (LOQ and 10 LOQ). Every recovery experiment was performed RESULTS five times for each water sample tested. Cocaine consumption in the southeast of Spain Estimation of consumption rates from biomarker was estimated once the metabolites were identified concentrations according to the equation proposed by Zuccato et al. Rates of consumption were estimated from (2008) (22). The quantification of benzoylecgonine biomarker levels in sewage samples (10, 14, 20) (cocaine metabolite) and cocaethylene (alcohol and which consisted in, firstly, to multiply the concen- cocaine concomitant consumption metabolite) by tration (ng/L) of each quantified metabolite in UPLCñqTOF-MS/MS (Fig. 1) showed the highest wastewater by the influent wastewater flow rate values at the weekend (Fig. 2). Sunday was the day (m3/day) coming from the study area (70% of total with the highest mass load value for benzoylecgo- flow) in order to calculate the amount of each nine (5.405 µg/L) followed by Friday (3.399 µg/L) metabolite that daily reach the sewage plant from and Saturday (2.444 µg/L). Results were statistical- the target area (g/day). The number of inhabitants ly significant (p < 0.001) for Sunday. Monday was served by the flow under study was calculated divid- the lowest value for benzoylecgonine (0.084 µg/L). ing these mass loads by the population served and As to cocaethylene, Saturday was the day of the using BOD parameter (Biochemical Oxygen week with the highest mass load value (0.083 µg/L), Demand). This parameter measures organic compo- followed by Sunday (0.049 µg/L) (Table 2). No nent of mainly domestic wastewater (kg/m3). Pre- significant interactions were recorded. vious studies have suggested that each inhabitant The total cocaine per day in the city of Murcia provides approximately 60 g of BOD per day (30). was calculated taking into account flow rate target Results are expressed in mg/day per 1000 inhabi- and benzoylecgonine concentration for each day tants. (Table 1), and applying a correction factor for The excretion rates of cocaine metabolites cocaine (Fig. 3). Total cocaine consumption in the were used to calculate the amount of the drug con- target area during the study (6 days) was 2463.74 sumed by the population under study. A correction milligrams per 1000 inhabitants, with a mean of factor used in previous studies (22) to back-calculate 410.6 milligrams per 1000 inhabitants and day. The from mass loads into amount of used illicit drug was highest cocaine intake was on Sunday, with a result applied. This correction factor considers the fraction of 889.97 milligrams of cocaine per day and 1000 of consumed parent drug normally excreted as a inhabitants, which is statistically significant (p < metabolite in urine, and the parent drug/excretion 0.001) when compared with the rest of the studied product molar mass ratio (4, 22). These calculations week. Friday is the day of the week with the second are only valid for drugs which produce the main highest consumption, with 629.4 milligrams per excretion product and therefore a reliable direct indi- 1000 inhabitants. Cocaine consumption in the city of Murcia (southeast of Spain) estimated by... 141

Figure 1. Identification of benzoylecgonine and cocaethylene by UPLCñqTOF-MS/MS

Figure 2. Amount of Benzoylecgonine and cocaethylene quantified for each analyzed day

Table 2. Benzoylecgonine and cocaethylene average concentrations of each analyzed day. Day (Benzoylecgonine) (µg/L) (Cocaethylene) (µg/L) Friday 3.399 n.q. Saturday 2.444 0.083 Sunday 5.405 0.049 Monday 0.084 0.023 Tuesday 2.302 0.014 Wednesday 0.582 0.031 Average 2.368 0.034 142 LUCÕA FERN¡NDEZ-L”PEZ et al.

Once the weekdays mean and the weekend Consequently, it is possible to calculate the mean were compared, an important difference arose. amount of cocaine doses consumed per day and In Murcia, the weekend mean was 644.7 mil- 1000 inhabitants. For that, it has to be assumed that ligrams/1000 people, whereas the weekdays mean 100 mg is an average dose (the equivalent of four was 176.55 milligrams/1000 people, which means 25 mg ìlinesî of cocaine) (31). that consumption during the weekend was 365.17% higher than during working-week days. Co-con- DISCUSSION AND CONCLUSION sumption was evaluated using the cocaethylene/ben- zoylecgonine ratio. The ratio was 0.014 and As cocaine consumption is increasing world- cocaethylene levels were higher at the weekend. wide, new accurate information about trends in con- A BOD parameter which measures organic sumption is essential to develop strategies to tackle the component wastewater (kg/m3) was employed to problem of drug abuse and to fight drug trafficking estimate the number of inhabitants that were at the (15, 32). Information about the type, scale, and demo- city during the period analyzed. Under the assump- graphics of cocaine consumption is needed in order to tion that each inhabitant provides approximately 60 g fully understand drug use patterns and to develop bet- of BOD per day, the number of inhabitants served ter methods and actions to reduce the problem (33-34). by the flow under study would be in an interval The use of cocaine, one of the most potent and between 194.316 and 253.250 (Table 3). The num- addictive illicit drugs, appears to be increasing in ber of inhabitants obtained is similar to that obtained some countries (14). Spain, together with the United from the census, around 250.000 inhabitants (in this Kingdom, Italy or Ireland, is one of the countries region is common to leave the City Centre in with the highest cocaine consumption according to Summer). the surveys (5).

Figure 3. Cocaine consumption in each analyzed day, in grams per day and 1000 inhabitants

Table 3. Inhabitants served by the wastewater flow target of each day.

3 Day Flow rate target (70%Qe) (m /day) BOD5 (mg/L) Inhabitants Friday 79.486 186 246.400 Saturday 72.944 171 207.883 Sunday 70.663 165 194.316 Monday 71.754 180 215.250 Tuesday 75.922 165 208.783 Wednesday 79.975 190 253.250 Cocaine consumption in the city of Murcia (southeast of Spain) estimated by... 143

According to a study that compared illicit drug weekend days (176.55 milligrams of cocaine per use in 19 European cities using the wastewater day and 1000 inhabitants) was 365.17% higher than analysis method, another city from the east of Spain on working weekdays. This pattern is similar in (Valencia) was the third city with the highest Nordic countries, which reflect a 300% increase cocaine consumption rate (34). If we compare our over the weekend (39) but far from the results for results with previous studies, cocaine consumption Barcelona or Santiago, around 60-80% and Milan in Murcia would be in higher than in Helsinki, (23%) (35, 39). These results do not match with the Zagreb, Oslo or Stockholm, lower than in London, epidemiological surveys in the entire country and Amsterdam, Zurich or Antwerp, and in Paris, Milan, suggest a different pattern in Spain according to the Dortmund, Lugano and Santiago, also than Spain. cityís demography. Our data showed that cocaine However, if we take into account sizes, political concentration at Sunday was twice the consumption importance and population, Murcia would fall of the following day. Regarding the weekdays, behind, i.e. Stockholm has more than 2 million Tuesday was the date when the regional festivity inhabitants, Oslo is around 1 million, and they are happened. These results showed that cocaine con- both European capitals. However, Murcia is only the sumption on Tuesday and Wednesday increased seventh largest city in Spain. Much more remark- again after Monday reduction. Since the urinary able is the comparison with Paris, which have near- elimination half-life of benzoylecgonine is nearly 4 ly 16 million inhabitants and a similar cocaine hours, the weekend increase would show the greater amount is consumed (22, 34, 35). If we consider the use of cocaine as a recreational drug. tendencies reported in the 2017 European survey (5) It is important to clarify that cocaine consump- we could find an explanation for these results, which tion is usually higher at nights and during weekends. is that Spain is one of the top countries in cocaine Therefore, cocaine concentrations of a specific day consumption together with the United Kingdom, would match with consumed cocaine the night and above Italy and France. before. As well, cocaine quantified on Friday, If we compare similar studies in other cities in Monday and Tuesday would correspond with con- Spain (36-37), Murcia would be the third city in sumed cocaine on Thursday, Sunday and Monday terms of cocaine consumption after Barcelona and night respectively. Thus, the highest cocaine con- Valencia, with similar consumption levels to sumption would occur on Thursday and Saturday Santiago and CastellÛn, with a similar population. It night. Thursdays in Murcia are the date on which should be noted that these results are similar to those university students usually go out. About the region- obtained from Molina de Segura in 2016 (562.2 mil- al festivity, it took place on a Monday night and a ligrams per 1000 inhabitants and day), a town close Tuesday in the morning. As a consequence, cocaine to Murcia (5). concentrations on Tuesday and Wednesday increa- Previous studies have shown a lower pattern of sed again. co-consumption of cocaine and alcohol. It has been Illicit drug use is a socially stigmatized and suggested that this pattern is much more common in often a hidden activity. As a consequence, tradition- Spain, which is in concordance with our results. Co- al survey methods such as general population survey consumption was evaluated using the cocaethyl- and interviews can be inaccurate and prone to con- ene/benzoylecgonine ratio. Our results were 0.014 jecture (34). It is also known that this kind of surveys for the whole week which is similar to previous underestimates results for illicit drugs with less con- results for Spanish cities of similar size to Santiago sumption, such as cocaine, and moreover, minors (35). Cocaethylene levels were higher during the usually experience some mistrust to the interlocutor weekend, which confirms a pattern of co-abused resulting in doubtful consumption answers (12). The substances. method used in this study is useful to estimate drugs Cocaine has been widely described as a recre- of abuse consumption in a population, since it allows ational drug and this pattern has been confirmed by to measure simultaneously illicit drugs and their recent surveys (5). According to this, cocaine con- metabolites in wastewater from a particular area, sumption should be higher during the weekends. In obtaining data of the most used drugs and consump- our study, sampling wastewater was analyzed on tion trends almost in real time, that is, within days or working days, one weekend, and one-day regional weeks, compared to surveys that may take years festivity. In our case, and like other studies (38), before publication (1, 34, 40). cocaine consumption was higher on weekend days, UPLC-QTOF MS is a powerful technique that with an average of 644.73 milligrams of cocaine per allows the detection and identification of several day and 1000 inhabitants. Cocaine consumption on widely consumed illicit drugs (41). It is a powerful 144 LUCÕA FERN¡NDEZ-L”PEZ et al. method that in our case has detected and quantified It is only an estimation based on a certain zone of cocaine and its metabolites every day of the study over a limited period, so further except for cocaethylene on Friday, offering a wide refinement of the methodology is needed. range of quantification, starting from 0.014 µg/L for Cocaine consumption levels obtained in the cocaethylene and 0.012 µg/L for benzoylecgonine. Region of Murcia or Spain are higher than levels In this study, we have obtained worthy results in obtained in similar studies carried out in the rest of terms of method validation what can be consulted Europe and the method used is useful for estimating through parameters as linearity, precision, accura- drugs consumption in a population. At the same cy, or the above commented LOQ and LOD. time, results are consistent with the results obtained UPLC-qTOF-MS/MS system has shown to be capa- in other Spanish cities of similar size. Wastewater ble of detecting and quantifying cocaine metabo- analysis provides more objective results and avoids lites in very hard conditions what gives support to several uncertainties related to surveys being possi- the idea of using this method in the future to quan- ble to study short-term consumption. Public admin- tify illicit drugs consumption of a community, but istration and citizens should be aware of the problem also, different pharmaceuticals or pollutants present that drugs of abuse represent. It is not only a health in water. public issue but also an economic problem due to This method is non-intrusive, objective and ED visits, hospitalization costs or detoxification does not require approval from individuals. When costs. Moreover, we think that, in order to reduce used for monitoring purposes in large populations, it consumption, public administration should carry out does not raise major ethical concerns because indi- more campaigns against drugs of abuse, warning cit- viduals are not identified and the prospects of harm- izens about their consequences. ing residents of catchment areas are remote (8, 42). In addition, this method is more cost effective and Conflict of interests does not have the problems of surveys that may suf- fer from a limited number of subjects and lack of There are no conflicts of interest to disclose. veracity in the responses. This is clearly a huge All the authors contributed to and have approved the advantage because it is very common that people do final manuscript. not trust their interlocutor altering the value of the responses. Besides, wastewater analysis provides an REFERENCES estimate of all the population contributing to the sewage over the sampling period (9). 1. 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According to 9. http://www.emcdda.europa.eu/stats13#dis- our data, total cocaine grams consumed in target play:/stats13/gpstab2b) 2013 (accessed 5. 06. area along analyzed days were 2463.74 milligrams. 2017). Cocaine consumption in the city of Murcia (southeast of Spain) estimated by... 145

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