Jaume Aceña

Pharmaceuticals and iodinated contrast media in a hospital wastewater: A case study to analyse their presence and characterise their environmental risk and hazard

This work analyses the presence of twenty-five pharmaceutical compounds belonging to seven different therapeutic groups and one iodinated contrast media (ICM) in a Spanish medium-size hospital located in the Valencia Region. Analysis of the target compounds in the hospital wastewater was performed by means of solid phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry analysis (HPLC-MS/MS). A screening level risk assessment combining the measured environmental concentrations (MECs) with dose-response data based on Predicted No Effect Concentration (PNEC) was also applied to estimate Hazard Quotients (HQs) for the compounds investigated. Additionally, the environmental hazard associated to the various compounds measured was assessed through the calculation of the Persistence, Bioaccumulation and Toxicity (PBT) Index, which categorizes compounds according to their environmentally damaging characteristics. The results of the study showed the presence of twenty-four out of the twenty-six compounds analysed at individual concentrations ranging from 5 ng L(-1) to 2 mg L(-1). The highest concentrations corresponded to the ICM iomeprol, found at levels between 424 and 2093 μg L(-1), the analgesic acetaminophen (15-44 μg L(-1)), the diuretic (DIU) furosemide (6-15 μg L(-1)), and the antibiotics (ABIs) ofloxacin and trimethoprim (2-5 μg L(-1)). The lowest levels corresponded to the anti-inflammatory propyphenazone, found at concentrations between 5 and 44 ng L(-1). Differences in terms of concentrations of the analysed compounds have been observed in all the therapeutic groups when comparing the results obtained in this and other recent studies carried out in hospitals with different characteristics from different geographical areas and in different seasons. The screening level risk assessment performed in raw water from the hospital effluent showed that the analgesics and anti-inflammatories (AAFs) acetaminophen, diclofenac, ibuprofen and naproxen, the antibiotics (ABIs) clarithromycin, ofloxacin and trimethoprim, and the β-blocker (BBL) propranolol were present at concentrations leading to HQ values higher than 10, thus indicating high risk. When applying a factor to take into account potential dilution and degradation processes, only the compound ibuprofen showed a HQ higher than 1. Likewise, the cumulative HQ or Toxic Units (TUs) calculated in the raw water for each of the therapeutic groups studied showed that these three classes of drugs were at concentrations high enough to potentially generate high risk to aquatic organisms while taking into account possible dilution and degradation processes only one of them, the AAFs can be considered to represent high risk. Finally, the environmental hazard assessment performed showed that the AAFs diclofenac and ibuprofen and the ABI clarithromycin have the highest, maximum value of 9 of PBT Index due to their inherent environmentally damaging characteristics of persistence, bioaccumulation and toxicity. The methodology followed in the present case study can be taken as a novel approach to classify and categorize pharmaceuticals on the basis of their occurrence in hospital effluents, their derived environmental risks, and their associated environmental hazard. This classification becomes important because it can be used as a model or orientation for hospitals in the process of developing environmentally sustainable policies and as an argument to justify the adoption of advanced, specific treatments for hospital effluents before being discharged into the public sewage system.

Pharmaceuticals and organic pollution mitigation in reclamation osmosis brines by UV/H2O2 and ozone.

One significant disadvantage of using reverse osmosis (RO) for reclamation purposes is the need to dispose of the RO retentates. These retentates contain a high concentration of micropollutants, effluent organic matter (EfOM) and other inorganic constituents, which are recalcitrant to biological treatment and may impact the environment. The occurrence of 11 pharmaceuticals (concentrations ranging from 0.2 to 1.6 μg L(-1)) and their mitigation in RO retentates by a UV/H2O2 process and ozonation was studied using a wide range of oxidant dosages. Eleven pharmaceuticals were identified at. Initial observed kinetic constants (kobs) were calculated for the different pharmaceuticals. Other typical wastewater parameters were also monitored during the UV/H2O2 and ozonation reactions. The range for kobs was found to be 0.8-12.8L mmol O3(-1) and 9.7-29.9 L mmol H2O2(-1) for the ozonation and UV/H2O2 process, respectively. For ozonation, Atenolol, Carbamazepine, Codeine, Trimethoprim and Diclofenac showed the lowest initial kobs (in the order mentioned). Atenolol and Carbamazepine appeared as the most ozone resistant pharmaceuticals, exhibiting the lowest percentage of elimination at low ozone doses. On the other hand, despite the non-selectivity of HO, differences in the initial kobs were also observed during the UV/H2O2 process. Trimethoprim, Paroxetine and Sulfamethoxazole exhibited the lowest initial kobs values (in the order mentioned). Trimethoprim and Paroxetine also exhibited the lowest percentage removal when low H2O2 doses were assayed. The compounds that were identified as problematic during ozonation were more efficiently removed by the UV/H2O2 process. UV/H2O2 generally appeared to be a more efficient technology for removing pharmaceuticals from RO brines compared to ozonation.

Concentration and risk of pharmaceuticals in freshwater systems are related to the population density and the livestock units in Iberian Rivers

Considerable amounts of pharmaceuticals are used in human and veterinary medicine, which are not efficiently removed during wastewater and slurries treatment and subsequently entering continuously into freshwater systems. The intrinsic biological activity of these non-regulated pollutants turns their presence in the aquatic environment into an ecological matter of concern. We present the first quantitative study relating the presence of pharmaceuticals and their predicted ecotoxicological effects with human population and livestock units. Four representative Iberian River basins (Spain) were studied: Llobregat, Ebro, Júcar and Guadalquivir. The levels of pharmaceuticals were determined in surface water and sediment samples collected from 77 locations along their stream networks. Predicted total toxic units to algae, Daphnia and fish were estimated for pharmaceuticals detected in surface waters. The use of chemometrics enabled the study of pharmaceuticals for: their spatial distribution along the rivers in two consecutive years; their potential ecotoxicological risk to aquatic organisms; and the relationships among their occurrence and predicted ecotoxicity with human population and animal farming pressure. The Llobregat and the Ebro River basins were characterized as the most polluted and at highest ecotoxicological risk, followed by Júcar and Guadalquivir. No significant acute risks of pharmaceuticals to aquatic organisms were observed. However potential chronic ecotoxicological effects on algae could be expected at two hot spots of pharmaceuticals pollution identified in the Llobregat and Ebro basins. Analgesics/antiinflammatories, antibiotics and diuretics were the most relevant therapeutic groups across the four river basins. Among them, hydrochlorothiazide and gemfibrozil, as well as azithromycin and ibuprofen were widely spread and concentrated pharmaceuticals in surface waters and sediments, respectively. Regarding their predicted ecotoxicity, sertraline, gemfibrozil and loratidine were identified as the more concerning compounds. Significantly positive relationships were found among levels of pharmaceuticals and toxic units and population density and livestock units in both surface water and sediment matrices.

Advances in liquid chromatography-high-resolution mass spectrometry for quantitative and qualitative environmental analysis.

This review summarizes the advances in environmental analysis by liquid chromatography–high-resolution mass spectrometry (LC–HRMS) during the last decade and discusses different aspects of their application. LC–HRMS has become a powerful tool for simultaneous quantitative and qualitative analysis of organic pollutants, enabling their quantitation and the search for metabolites and transformation products or the detection of unknown compounds. LC–HRMS provides more information than low-resolution (LR) MS for each sample because it can accurately determine the mass of the molecular ion and its fragment ions if it can be used for MS–MS. Another advantage is that the data can be processed using either target analysis, suspect screening, retrospective analysis, or non-target screening. With the growing popularity and acceptance of HRMS analysis, current guidelines for compound confirmation need to be revised for quantitative and qualitative purposes. Furthermore, new commercial software and user-built libraries are required to mine data in an efficient and comprehensive way. The scope of this critical review is not to provide a comprehensive overview of the many studies performed with LC–HRMS in the field of environmental analysis, but to reveal its advantages and limitations using different workflows.

Light-induced catalytic transformation of ofloxacin by solar Fenton in various water matrices at a pilot plant: Mineralization and characterization of major intermediate products ☆

This work investigated the application of a solar driven advanced oxidation process (solar Fenton), for the degradation of the antibiotic ofloxacin (OFX) in various environmental matrices at a pilot-scale. All experiments were carried out in a compound parabolic collector pilot plant in the presence of doses of H2O2 (2.5 mg L(-1)) and at an initial Fe(2+) concentration of 2 mg L(-1). The water matrices used for the solar Fenton experiments were: demineralized water (DW), simulated natural freshwater (SW), simulated effluent from municipal wastewater treatment plant (SWW) and pre-treated real effluent from municipal wastewater treatment plant (RE) to which OFX had been spiked at 10 mg L(-1). Dissolved organic carbon removal was found to be dependent on the chemical composition of the water matrix. OFX mineralization was higher in DW (78.1%) than in SW (58.3%) at 12 mg L(-1) of H2O2 consumption, implying the complexation of iron or the scavenging of hydroxyl radicals by the inorganic ions present in SW. On the other hand, the presence of dissolved organic matter (DOM) in SWW and RE, led to lower mineralization per dose of H2O2 compared to DW and SW. The major transformation products (TPs) formed during the solar Fenton treatment of OFX, were elucidated using liquid chromatography-time of flight-mass spectrometry (LC-ToF-MS). The transformation of OFX proceeded through a defluorination reaction, accompanied by some degree of piperazine and quinolone substituent transformation while a hydroxylation mechanism occurred by attack of the hydroxyl radicals generated during the process leading to the formation of TPs in all the water matrices, seven of which were tentatively identified. The results obtained from the toxicity bioassays indicated that the toxicity originates from the DOM present in RE and its oxidation products formed during the photocatalytic treatment and not from the TPs resulted from the oxidation of OFX.

Ibuprofen exposure in Lemna gibba L.: Evaluation of growth and phytotoxic indicators, detection of ibuprofen and identification of its metabolites in plant and in the medium

Ibuprofen (IBU) is detected worldwide in water bodies due to the incomplete removal by wastewater treatments. Contrasting results have been reported on the toxicity of IBU on aquatic biomonitor plants such as duckweed, and no data about IBU detection and metabolism in plants has been reported. In this work, the effects of 1 mg L(-1) IBU on Lemna gibba L. were monitored in an 8-day laboratory test. In particular, an increase in frond number (+12%) and multiplication rate (+10%) while no variations in photosynthetic pigment content were observed. Moreover, UPLC-HRMS analysis of the presence of IBU and its metabolites in plants and in the growth medium was performed. The results showed that, besides IBU, 11 IBU metabolites were detected in plants. Among the IBU metabolites, hydroxyl- and dihydroxyl-IBU were found, whereas carboxyl-IBU was undetectable. Interestingly, some IBU metabolites were detected in the plant growth solution at the end of the IBU treatment, while no IBU products were found in the IBU solution without plants, suggesting a role for L. gibba in IBU metabolism. The findings of this work represent an important step for a better evaluation of the effects of IBU and its metabolites in duckweed, with notable implications for the eco-toxicological assessment of IBU in the aquatic ecosystem.

Study of pharmaceuticals in surface and wastewater from Cuernavaca, Morelos, Mexico: Occurrence and environmental risk assessment

The present work describes the first known study to date on the occurrence of pharmaceuticals in surface water and wastewater of Cuernavaca, the capital of the state of Morelos (México). Selected pharmaceuticals (a total of 35) were extracted from the collected water samples with a generic solid phase extraction (SPE) protocol and determined in the sample extracts by means of high-performance liquid chromatography coupled to electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS). A screening level risk assessment combining the measured environmental concentrations (MECs) with dose-response data based on predicted no-effect concentrations (PNECs) was also applied to estimate Hazard Quotients (HQs) for the pharmaceuticals detected in the investigated area. A total of twelve pharmaceuticals were found in the water samples analyzed, with detection frequencies above 78% and in most cases of 100%. Overall, the most abundant pharmaceuticals in surface water were the analgesic and anti-inflammatory drugs naproxen (732-4880ng/L), acetaminophen (354-4460ng/L), and diclofenac (258-1398ng/L), and the lipid regulator bezafibrate (286-2100ng/L). On the contrary, other compounds like the β-blocker atenolol and the psychiatric drug carbamazepine were found at only a few ng or tens of ng per liter in the Apatlaco River. Despite the fact that some of the most abundant compounds showed good removal (>97%) during wastewater treatment, concentrations downstream the WWTP were only slightly lower than upstream. This indicates the existence of additional inputs of untreated wastewater into the river. Based on the obtained HQ-values, the concentrations of ibuprofen, sulfamethoxazole, diclofenac and naproxen present in the river could pose a high toxicity risk for the aquatic ecosystem. These findings highlight these pharmaceuticals as relevant organic contaminants in the area of study and the need to further monitor them in order to adopt appropriate measures to safeguard the ecosystem, and eventually human health.

Identification of phototransformation products of sildenafil (Viagra) and its N‐demethylated human metabolite under simulated sunlight

Recent publications on pharmaceutical monitoring are increasingly covering the field of illicit drugs and lately the forensic evaluation of designing illegal analogs of lifestyle drugs like the phosphodiesterase type 5 (PDE-5) inhibitors Viagra (sildenafil), Levitra (vardenafil) and Cialis (tadalafil). Recently, the presence of all three erectile dysfunction treatment drugs has been reported in wastewaters at very low concentrations. In the environment, contaminants undergo various physical or chemical processes classified into abiotic (photolysis, hydrolysis) and biotic (biodegradation) reactions. Thus, changes in the chemical structure lead to the formation of new transformation products, which may persist in the environment or be further degraded. This study describes the photolysis of sildenafil (SDF) and its human metabolite N-demethylsildenafil (DM-SDF) under simulated solar radiation (Xenon lamp). Following chromatographic separation of the irradiated samples, eight photoproducts in the SDF samples and six photoproducts for DM-SDF were detected and characterized. The combination of ultra performance liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry (UPLC-ESI-QToF-MS), liquid chromatography-atmospheric pressure chemical ionization-triple quadrupole mass spectrometry (LC-APCI-QqQ-MS) and hydrogen/deuterium-exchange experiments allowed to propose plausible chemical structures for the photoproducts, taking into account the characteristic fragmentation patterns and the accurate mass measurements. These mass spectral data provided sound evidence for the susceptibility of the piperazine ring toward photodegradation. A gradual breakdown of this heterocyclic structure gave rise to a series of products, which in part were identical for SDF and DM-SDF. The sulfonic acid, as the formal product of sulfonamide hydrolysis, was identified as key intermediate in the photolysis pathway. In both drug/metabolite molecules, phototransformation processes taking place beyond the sulfonamide group were deemed to be of minor relevance.

The in vitro interference of synthetic progestogens with carp steroidogenic enzymes.

Synthetic progestogens represent a class of pharmaceuticals widely used in oral contraceptives and in hormone replacement therapies. They reach the aquatic environment through wastewater effluents; however, environmental concentrations and effects on non-target organisms are poorly known. Given the important role of progestogens regulating fish spawning processes, this study aimed at assessing the in vitro interference of four currently used progestogens-drospirenone (DRO), levonorgestrel (LNG), norethindrone (NOR) and cyproterone acetate (CPA) - with key enzymatic activities involved in the synthesis of active steroids in carp (Cyprinus carpio). The enzymatic pathways investigated were (a) CYP17 (C17,20-lyase) and CYP11β involved in the synthesis of androgens, (b) CYP19 that catalyses the aromatization of androgens to estrogens, and (c) 20β-hydroxysteroid dehydrogenase (20β-HSD) responsible for the synthesis of maturation-inducing hormones. All tested progestogens significantly inhibited the synthesis of androgens: DRO (IC50: 3.8 μM) was the strongest inhibitor of CYP17 followed by CPA (IC50s: 183 μM). Moreover, NOR (IC50: 0.4 μM), DRO (IC50: 1.8 μM) and CPA (IC50s: 87 μM) inhibited CYP11β. An inhibition by NOR of ovarian CYP19 activity, and by DRO and CPA of 20β-HSD was also observed, but at rather high concentrations (500 μM). Overall, this study highlights the potential of synthetic progestogens, and particularly DRO and NOR, to interfere with the biosynthesis of androgens in carp gonads.

Structure elucidation of phototransformation products of unapproved analogs of the erectile dysfunction drug sildenafil in artificial freshwater with UPLC-Q Exactive-MS

In this study, four unapproved analogues of Sildenafil (SDF) were photodegraded under synthetic sunlight in artificial freshwater. Homosildenafil (H-SDF), hydroxyhomo-sildenafil (HH-SDF), norneosildenafil (NR-SDF) and thiosildenafil (T-SDF) were selected because they are frequently detected as adulterants in natural herbal products. Using UPLC-Orbitrap (Q Exactive)-MS, six photoproducts common to H-SDF, HH-SDF and T-SDF and nine unique transformation products of different molecular weights were identified based on their high-resolution (+)ESI product ion spectra. Mass spectral analysis of deuterated H-SDF, labeled on the N-ethyl group, allowed to gain mechanistic insight into the fragmentation pathway of the substituted piperazine ring and to support the postulated photoproduct structures. The mass spectral fragmentation confirmed the stepwise destruction of the piperazine ring eventually producing a sulfonic acid derivative (C17 H20 N4 O5 S: 392.1151 Da). In contrast, the photodegradation of NR-SDF, which lacks a piperazine ring in its structure, formed only two prominent photoproducts originating from N,N-dealkylation of the sulfonamide followed by hydrolysis. The current work constitutes the first study on the photodegradation of analogs of erectile dysfunction drugs and the first detection of two transformation products (m/z 449 and 489) in environmental samples.