Laura Ferrando-Climent

Determination of 81 pharmaceutical drugs by high performance liquid chromatography coupled to mass spectrometry with hybrid triple quadrupole-linear ion trap in different types of water in Serbia.

The aim of the work was to study the occurrence of pharmaceuticals in waste, surface, underground, and drinking water samples collected in Serbia. A multi-residue method for the analysis of 81 pharmaceutical drugs from different therapeutic classes in the various types of water was applied. Twenty-five composite water samples were prepared using solid-phase extraction and the presence of 81 pharmaceutical compounds in the extracts was analyzed by ultra-high performance liquid chromatography coupled to mass spectrometry with hybrid triple quadrupole-linear ion trap (UPLC-QqLIT-MS/MS). Forty seven compounds of 81 drugs were found in four different types of analyzed water. The highest concentrations of ibuprofen of 20.1 μg L(-1), 10,11-epoxycarbamazepine of 16.2 μg L(-1), 2-hydroxycarbamazepine of 15.9 μg L(-1) and acetaminophen of 15.7 μg L(-1) were found in municipal waste water sample. Results revealed the presence of salicylic acid in 41.67% of water samples, carbamazepine in 36.11%, propranolol and irbesartan in 30.56%. The obtained results were discussed in relation to the relevant data available in literature. This is the first attempt to assess the occurrence of these 81 pharmaceutical residues in water samples in Serbia.

Comprehensive study of ibuprofen and its metabolites in activated sludge batch experiments and aquatic environment

Even though Ibuprofen is one of the most studied pharmaceutical in the aquatic environment, there is still a lack of information about its fate and the generation of different transformation products along wastewater treatment plants (WWTPs). Ibuprofen biotransformation products can be generated by human metabolism or by microorganisms present in WWTPs and in natural waters, soils, and sediments, which increase the probability to find them in environment. In this work, the presence of ibuprofen and its main metabolites: ibuprofen carboxylic acid (CBX IBU), 2-hydroxylated ibuprofen (2-OH IBU) and 1-hydroxylated ibuprofen (1-OH IBU), was monitored quantitatively along the biodegradation processes occurring in different batch activated sludge (BAS) experiments under different working conditions. Total ibuprofen removal, achieved in almost all the experiments, was related in part to the formation of the metabolites mentioned. Another ibuprofen metabolite, 1,2-dihydroxy ibuprofen, was detected in BAS experiments for the first time. The metabolites 2-OH IBU and 1-OH IBU remained in solution at the end of ibuprofen biodegradation experiments whereas CBX IBU disappeared faster than hydroxylated metabolites. In addition, also the biodegradation of 1-OH IBU, 2-OH IBU and CBX IBU was evaluated in batch experiments: CBX IBU removal occurred at the highest rate followed by IBU, 2-OH IBU, and 1-OH IBU, which exhibited the lowest removal rate. Finally, Ibuprofen and ibuprofen metabolites were monitored in sewage and natural water samples, where they were found at higher levels than expected: the maximum concentration in influent wastewater samples were 13.74, 5.8, 38.4, 94.0μg/L for IBU, 1-OH IBU, CBX IBU and 2-OH IBU respectively; whereas maximum levels in effluent wastewater samples were 1.9, 1.4, 10.7, 5.9 μg/L for IBU, 1-OH IBU, CBX IBU and 2-OH IBU respectively. High levels of the compounds were also found in river samples, in particular for CBX IBU, which was detected up to 3.9 μg/L.

Degradation of pharmaceuticals in non-sterile urban wastewater by Trametes versicolor in a fluidized bed bioreactor

The constant detection of pharmaceuticals (PhACs) in the environment demonstrates the inefficiency of conventional wastewater treatment plants to completely remove them from wastewaters. So far, many studies have shown the feasibility of using white rot fungi to remove these contaminants. However, none of them have studied the degradation of several PhACs in real urban wastewater under non-sterile conditions, where mixtures of contaminants presents at low concentrations (ng L(-1) to μg L(-1)) as well as other active microorganisms are present. In this work, a batch fluidized bed bioreactor was used to study, for the first time, the degradation of PhACs present in urban wastewaters at their pre-existent concentrations under non-sterile conditions. Glucose and ammonium tartrate were continuously supplied as carbon and nitrogen source, respectively, and pH was maintained at 4.5. Complete removal of 7 out of the 10 initially detected PhACs was achieved in non-sterile treatment, while only 2 were partially removed and 1 of the PhACs analyzed increased its concentration. In addition, Microtox test showed an important reduction of toxicity in the wastewater after the treatment.

Effects on activated sludge bacterial community exposed to sulfamethoxazole.

The bacterial community shift on a lab scale Sequencing Batch Reactor (SBR) fed with synthetic wastewater and exposed to 50μgL(-1) of sulfamethoxazole (SFX) for 2months was investigated in this study. The impact on biological nutrient removal performance and SFX removal efficiencies were also studied. Satisfactory biological nutrient removal was observed as regards to COD and Nitrogen. SFX removal efficiencies ranged between 20% and 50% throughout the experimental period, enhanced within the aerobic phases of the SBR cycle, with no evident signs of biomass acclimation. Nevertheless, denaturing gradient gel electrophoresis (DGGE) analysis showed significant variance leading to not only the fading, but also the emergence of new species in the bioreactor bacterial community after SFX dosage. According to the phylogenetic analysis, bacteria belonging to Betaproteobacteria and Gammaproteobacteria classes were the dominant species, among them, the Thiotrix spp. (Gammaproteobacteria) cell number increased due to its tolerance to the antibiotic. On the other hand, the classes Sphingobacteria, Actinobacteria, Chloroflexi and Chlorobi were found to be more vulnerable to the antibiotic load and disappeared. The sulphonamide resistance gene sulI was also quantified and discussed, as there are very few studies on bacterial resistance in lab-scale treatment reactors.

Removal of ibuprofen and its transformation products: experimental and simulation studies.

Pharmaceutically active compounds (PhACs) deserve attention because of their effect on ecosystems and human health, as well as their continuous introduction into the aquatic environment. Classification schemes are suggested to characterise their biological degradation, e.g., based on pseudo-first-order kinetics, but these schemes can vary significantly, presumably due to pharmaceutical loads, sludge characteristics and experimental conditions. Degradation data for PhAC transformation products (TPs) are largely lacking. The present work focuses not only on the biodegradation of the pharmaceutical compound ibuprofen but also on its best-known TPs (i.e., carboxyl ibuprofen and both hydroxyl ibuprofen isomers). Ibuprofen is one of the most commonly consumed PhACs and can be found in different environmental compartments. The experiment performed consisted of a set of aerated batch tests with different suspended solid and ibuprofen concentrations to determine the influence of these parameters on the calculated biodegradation constant (K(biol)). Sampling of the liquid phase at different scheduled times was assessed, removal efficiencies were calculated and pseudo-first-order kinetics were adjusted to obtain experimental K(biol) values for the parent compound and its TPs. The experimental data were successfully fitted to ASM-based models, with K(biol) values for the target compounds ranging from almost 1 to 17 L gSST(-1) d(-1), depending on the concentrations of the biomass and ibuprofen. This work provides innovative knowledge not only regarding the removal of TPs but also the formation kinetics of these TPs.

Non conventional biological treatment based on Trametes versicolor for the elimination of recalcitrant anticancer drugs in hospital wastewater

This work presents a study about the elimination of anticancer drugs, a group of pollutants considered recalcitrant during conventional activated sludge wastewater treatment, using a biological treatment based on the fungus Trametes versicolor. A 10-L fluidized bed bioreactor inoculated with this fungus was set up in order to evaluate the removal of 10 selected anticancer drugs in real hospital wastewater. Almost all the tested anticancer drugs were completely removed from the wastewater at the end of the batch experiment (8 days) with the exception of Ifosfamide and Tamoxifen. These two recalcitrant compounds, together with Cyclophosphamide, were selected for further studies to test their degradability by T. versicolor under optimal growth conditions. Cyclophosphamide and Ifosfamide were inalterable during batch experiments both at high and low concentration, whereas Tamoxifen exhibited a decrease in its concentration along the treatment. Two positional isomers of a hydroxylated form of Tamoxifen were identified during this experiment using a high resolution mass spectrometry based on ultra-high performance chromatography coupled to an Orbitrap detector (LTQ-Velos Orbitrap). Finally the identified transformation products of Tamoxifen were monitored in the bioreactor run with real hospital wastewater.

Suspect screening of emerging pollutants and their major transformation products in wastewaters treated with fungi by liquid chromatography coupled to a high resolution mass spectrometry

A new approach for the screening of 33 pharmaceuticals and 113 of their known transformation products in wastewaters was developed. The methodology is based on the analysis of samples by liquid chromatography coupled to high resolution mass spectrometry (HRMS) followed by data processing using specific software and manual confirmation. A home-made library was built with the transformation products reported in literature for the target pharmaceuticals after treatment with various fungi. The method was applied to the search of these contaminants in 67 samples generated along treatment of wastewaters with white-rot fungus Trametes versicolor. The screening methodology allowed the detection of different transformation products (TPs) generated from degradation of parent compounds after fungal treatment. This approach can be a useful tool for the rapid screening and tentative detection of emerging contaminants during water treatment in both full and batch-scale studies when pure standards are not available.

Identification of markers of cancer in urban sewage through the use of a suspect screening approach

The administration of anticancer drugs during chemotherapy treatments has increased considerably in recent years, and based on the growing incidence of cancer worldwide there is a foreseen increase in their use over the coming years. Many anticancer drugs are not removed by conventional wastewater treatment plants (WWTPs) and can therefore reach the aquatic environment and potentially threaten aquatic life. The objective of this work was to apply a suspect screening methodology to detect chemotherapy and radiotherapy drugs and their related compounds such metabolites and/or biomarkers in wastewater. The use of logical pre-determined criteria to refine the suspect list down to a relatively small number of relevant compounds greatly improved the efficiency of the analysis. Mass accuracy, isotopic patterns and predicted retention time were used to tentatively identify the suspects. Successful identification of cancer-related suspects included two antineoplastic hormones, two X-ray contrast agents and a pyrrolizidine alkaloid related to an herbal medicine. This is the first time that a suspect screening paradigm has been successfully applied to the identification of pharmaceuticals and biomarkers related to chemotherapy in wastewater.

Occurrence and Risks of Contrast Agents, Cytostatics, and Antibiotics in Hospital Effluents

During the past 20 years, the presence of pharmaceutical active compounds (PhACs) in the water bodies has been gaining increasing attention and nowadays there is a broad acknowledgment on their consideration as an emerging environmental problem. As a response to this threat, regulatory agencies and the European Commission have implemented a regulatory framework for environmental risk assessment (ERA) of PhACs. One of the main sources of pharmaceuticals in the environment is connected to the hospital discharge into the urban system including the antibiotic resistances and large number of pathogens. Despite wastewater is normally collected and delivered to wastewater treatment plants, it has been demonstrated that the regular treatments applied in such facilities are not completely effective through a variety of pharmaceuticals that are subsequently introduced into the environment. In this document, the authors explore the occurrence in hospital wastewater and the environmental risks of three relevant pharmaceutical groups: cytostatics, antibiotics, and contrast agents.