Mira Petrovic

Tracing Pharmaceutical Residues of Different Therapeutic Classes in Environmental Waters by Using Liquid Chromatography/Quadrupole-Linear Ion Trap Mass Spectrometry and Automated Library Searching

This article describes the development, optimization, and validation of an analytical method for the simultaneous detection and identification of 73 pharmaceutical residues, covering various therapeutic groups, in both surface and wastewaters. The method is based on the simultaneous extraction of all target compounds by Solid Phase Extraction (SPE), using a hydrophilic-lipophilic balanced polymer followed by liquid chromatography tandem mass spectrometry, using a hybrid triple quadrupole-linear ion trap mass spectrometer (QqLIT). Quantitative analysis was performed using the 4000 Qtrap tandem mass spectrometer in Selected Reaction Monitoring (SRM) mode, monitoring two SRM transitions to fulfill EC guidelines, as well as to ensure an accurate identification of target compounds in the samples. Quantitation is performed by the internal standard approach, indispensable to correct matrix effects. Moreover, to obtain an extra tool for confirmation and identification of the studied pharmaceuticals, an Information Dependent Acquisition (IDA) experiment was performed, with SRM as the survey scan and an enhanced product ion (EPI) scan, at three different collision energies, as dependent scan. Compound identification was carried out by library search with a developed library, created by the infusion of standards, based on EPI spectra at the three collision energies. The main advantages of the developed method, besides high sensitivity (limits of detection ranging from 0.1-55 ng/L, depending on the matrix), selectivity, and reliability of results, are that all compounds are extracted in a single step, speeding up considerably sample preparation. Recoveries obtained were generally higher than 50% for both surface and wastewaters, with the exception of metronidazole (20-30%), salbutamol (33-43%), atorvastatin (40% in surface water), and nadolol (31% in surface water) that yielded lower but still acceptable recoveries. The overall variability of the method was below 15%, for all compounds and all matrixes tested. Finally, the method developed has been applied to the analysis of various influent and effluent wastewaters as well as river waters from Spain.

Wastewater treatment plants as a pathway for aquatic contamination by pharmaceuticals in the Ebro river basin (Northeast Spain)

The occurrence of 28 pharmaceuticals of major human consumption in Spain, including analgesics and anti-inflammatories, lipid regulators, psychiatric drugs, antibiotics, antihistamines, and beta-blockers, was assessed along the Ebro river basin, one of the biggest irrigated lands in that country. Target compounds were simultaneously analyzed by off-line solid-phase extraction, followed by liquid chromatography-tandem mass spectrometry. The loads of detected pharmaceuticals and their removal rates were studied in seven wastewater treatment plants (WWTPs) located in the main cities along the basin. Total loads ranged from 2 to 5 and from 0.5 to 1.5 g/d/1,000 inhabitants in influent and effluent wastewaters, respectively. High removal rates (60-90%) were achieved mainly for analgesics and anti-inflammatories. The other groups showed lower rates, ranging from 20 to 60%, and in most cases, the antiepileptic carbamazepine, macrolide antibiotics, and trimethoprim were not eliminated at all. Finally, the contribution of WWTP effluents to the presence of pharmaceuticals in receiving river waters was surveyed. In receiving surface water, the most ubiquitous compounds were the analgesics and anti-inflammatories ibuprofen, diclofenac, and naproxen; the lipid regulators bezafibrate and gemfibrozil; the antibiotics erythromycin, azithromycin, sulfamethoxazole, trimethoprim, and less frequently, ofloxacin; the antiepileptic carbamazepine; the antihistamine ranitidine; and the beta-blockers atenolol and sotalol. Although levels found in WWTP effluents ranged from low microg/L to high ng/L, pharmaceuticals in river waters occurred at levels at least one order of magnitude lower (low ng/L range) because of dilution effect. From the results obtained, it was proved that WWTP are hot spots of aquatic contamination concerning pharmaceuticals of human consumption.

Occurrence and distribution of pharmaceuticals in surface water, suspended solids and sediments of the Ebro river basin, Spain.

The occurrence of 43 pharmaceuticals belonging to predominant therapeutic classes and their distribution in surface water, suspended solids and sediments has been investigated in the Ebro river basin in the Northeast of Spain. WWTP effluents were found to be a main source of contamination and the spatial distribution was affected by the river flow at the sampling point and corresponding dilution factor, resulting in higher concentrations and higher loads in small tributary rivers than in the Ebro river. The study showed that some compounds are preferentially found bound to suspended solids and not detected in river water. Generally, compounds with basic characteristics (pKa > 7) showed higher tendency to bind to suspended solids. The sediment samples generally presented lower concentrations than suspended solids.

Ultrasonic solvent extraction of pesticides from soil

Ultrasonic solvent extraction of the pesticides atrazine, propham, chlorpropham, diflubenzuron, α-cypermethrin and tetramethrin from soil is reported. The extraction procedure was optimized with regard to the amount of solvent, the duration of sonication and the number of extraction steps. Ultrasonic solvent extraction was compared with traditional extraction methods, shake-flask and Soxhlet extraction. The recovery of pesticides was determined by quantitative thin-layer chromatography on RP-18 plates. Ultrasonic extraction using acetone showed satisfactory extraction efficiencies combined with simplicity of use and low solvent consumption.

Pharmaceuticals in Drinking Water

Pharmaceuticals are a group of emerging contaminants that has received noticeable attention over the past decade. Continual development of the advanced instruments and improved analytical methodologies made possible detection of these microcontaminants in low levels in different environmental matrices. Traces of pharmaceuticals have also been found in groundwater and surface water that are used for drinking water supply. Therefore, concern has been raised over the potential risk to human health from exposure to the pharmaceutical residues via drinking water. Still, there is no evidence that any serious risk could arise from low concentrations of pharmaceuticals found in drinking water. Anyhow, there is much more to be understood about long-term, low-level exposure to a mixture of pharmaceuticals and their metabolites. In the following chapter, we give a brief overview of the technologies commonly applied for drinking water treatment, with reference to pharmaceutical removal, and we review available literature data on the occurrence of pharmaceuticals in finished drinking water.

Degradation of carbamazepine by Trametes versicolor in an air pulsed fluidized bed bioreactor and identification of intermediates.

The paper describes the aerobic degradation of carbamazepine (CBZ), an anti-epileptic drug widely found in aquatic environment, from Erlenmeyer flask to bioreactor by the white-rot fungus Trametes versicolor. In Erlenmeyer flask, CBZ at approximately 9xa0mgxa0L(-1) was almost completely eliminated (94%) after 6xa0d, while at near environmentally relevant concentrations of 50xa0μgxa0L(-1), 61% of the contaminant was degraded in 7xa0d. Acridone, acridine, 10,11-dihydro-10,11-dihydroxy-CBZ, and 10, 11-epoxy-CBZ were identified as major metabolites, confirming the degradation of CBZ. The degradation process was then carried out in an air pulsed fluidized bioreactor operated in batch and continuous mode. Around 96% of CBZ was removed after 2 days in batch mode operation, and 10,11-dihydro-10,11-epoxycarbamazepine was found as unique metabolite. In bioreactor operated in continuous mode with a hydraulic retention time of 3xa0d, 54% of the inflow concentration (approx. 200xa0μgxa0L(-1)) was reduced at the steady state (25xa0d) with a CBZ degradation rate of 11.9xa0μgxa0CBZxa0g(-1) dry weight d(-1). No metabolite was detected in the culture broth. Acute toxicity tests (Microtox) indicated that the final culture broth in both batch and continuous mode operation were non toxic, with 15xa0min EC50 values of 24% and 77%, respectively.

Occurrence and Elimination of Pharmaceuticals During Conventional Wastewater Treatment

Pharmaceuticals have an important role in the treatment and prevention of disease in both humans and animals. Since they are designed either to be highly active or interact with receptors in humans and animals or to be toxic for many infectious organisms, they may also have unintended effects on animals and microorganisms in the environment. Therefore, the occurrence of pharmaceutical compounds in the environment and their potential effects on human and environ- mental health has become an active subject matter of actual research. There are several possible sources and routes for pharmaceuticals to reach the environment, but wastewater treatment plants have been identified as the main point of their collection and subsequent release into the environment, via both effluent wastewater and sludge. Conventional systems that use an activated sludge process are still widely employed for wastewater treatment, mostly because they produce effluents that meet required quality standards (suitable for disposal or recycling purposes), at reasonable operating and maintenance costs. However,

Hospital wastewater treatment by fungal bioreactor: removal efficiency for pharmaceuticals and endocrine disruptor compounds.

Hospital effluents contribute to the occurrence of emerging contaminants in the environment due to their high load of pharmaceutical active compounds (PhACs) and some endocrine disruptor compounds (EDCs). Nowadays, hospital wastewaters are co-treated with urban wastewater; however, the dilution factor and the inefficiency of wastewater treatment plants in the removal of PhACs and EDCs make inappropriate the co-treatment of both effluents. In this paper, a new alternative to pre-treat hospital wastewater concerning the removal of PhACs and EDCs is presented. The treatment was carried out in a batch fluidized bed bioreactor under sterile and non-sterile conditions with Trametes versicolor pellets. Results on non-sterile experiments pointed out that 46 out of the 51 detected PhACs and EDCs were partially to completely removed. The total initial PhAC amount into the bioreactor was 8185 μg in sterile treatment and 8426 μg in non-sterile treatment, and the overall load elimination was 83.2% and 53.3% in their respective treatments. In addition, the Microtox test showed reduction of wastewater toxicity after the treatment. Hence, the good efficiency of the fungal treatment regarding removal of the wide diversity of PhACs and EDCs detected in hospital effluents is demonstrated.

Tracing pharmaceuticals in a municipal plant for integrated wastewater and organic solid waste treatment

The occurrence and removal of 42 pharmaceuticals, belonging to different therapeutic groups (analgesics and anti-inflammatory drugs, anti-ulcer agent, psychiatric drugs, antiepileptic drug, antibiotics, ß-blockers, diuretics, lipid regulator and cholesterol lowering statin drugs and anti-histamines), were studied in the wastewater and sewage sludge trains of a full scale integrated treatment plant. The plant employs a biological nutrient removal (BNR) process for the treatment of municipal wastewater, and a single-stage mesophilic anaerobic co-digestion for the treatment of wasted activated sludge mixed with the organic fraction of municipal solid waste (OFMSW), followed by a short-cut nitrification-denitrification of the anaerobic supernatant in a sequential batch reactor. Influent and effluent wastewater, as well as thickened, digested and treated sludge were sampled and analyzed for the selected pharmaceuticals in order to study their presence and fate during the treatment. Twenty three compounds were detected in influent and effluent wastewater and eleven in sludge. Infiltration of groundwater in the sewer system led to a dilution of raw sewage, resulting in lower concentrations in wastewater (up to 0.7 μg/L in influent) and sludge (70 ng/g d.w.). Due to the dilution, overall risk quotient for the mixture of pharmaceuticals detected in effluent wastewater was less than one, indicating no direct risk for the aquatic environment. A wide range of removal efficiencies during the treatment was observed, i.e. <20% to 90%. The influent concentrations of the target pharmaceuticals, as polar compounds, were undoubtedly mostly affected by BNR process in the wastewater train, and less by anaerobic-co-digestion. Mass balance calculations showed that less than 2% of the total mass load of the studied pharmaceuticals was removed by sorption. Experimentally estimated distribution coefficients (<500 L/kg) also indicated that the selected pharmaceuticals preferably remain in the aqueous phase, and that biodegradation/transformation is the primary removal mechanism for these compounds during wastewater treatment.

A survey of emerging contaminants in the estuarine receiving environment around Auckland, New Zealand

Increasing urbanisation in the future will put mounting stresses on the receiving environments around those urban centres due to increased sedimentation and contaminant runoff. Emerging contaminants (ECs) are an extensive array of chemicals and many are not under regulatory action. Within New Zealand likely future pressures from ECs will be in both urban centres and rural areas due to intensive agriculture, although at present there is a lack of information on the state of the environment in both sectors. This study was initiated to gauge the distribution of ECs in the urban environment by measuring concentrations of flame retardants, plasticisers, alkylphenols, herbicides and pesticides, steroid oestrogens, pharmaceuticals and heavy metals in sediment from 13 estuarine sites around Auckland, New Zealands biggest city. Total polybrominated diphenyl ether (PBDE) flame retardant concentrations ((7)ΣPBDE) ranged from 0.55 to 573 ng/g (dw). The phthalate plasticiser di(2-ethylhexyl)phthalate (DEHP) was measured at up to 11,500 ng/g from one site. Nonylphenol (NP) was found at up to 32,000 ng/g at one site adjacent to the citys major wastewater treatment plant (WWTP). However, median concentrations of NP were 153 ng/g, suggesting this site was not representative of the region. Nonylphenol mono- and di-ethoxylates (NPEO1,2) had highest concentrations (1600 ng/g) at a marina. Highest glyphosate concentrations (up to 950 ng/g) were observed at residential sites. Steroid oestrogens were detected at extremely low concentrations (maximum 2.2 ng/g), while all other pesticides or herbicides were not detected at any sites. Multi-residue analysis of 46 pharmaceuticals showed presence of 21 compounds at one or more sites, with average concentrations ranging from 0.16 to 7.66 ng/g. Generally, environmental concentrations of ECs were similar to those reported world-wide. However, comparisons for pharmaceuticals were problematic, due to very few studies on pharmaceutical concentrations in estuarine sediments, with most focussed on sewage and stream water phases.