Pharmaceuticals In Sewage Sludge Research Articles

Application of QuEChERS extraction and LC–MS/MS for determination of pharmaceuticals in sewage sludges sampled across the Czech Republic

The use of pharmaceuticals entails a significant risk of environmental contamination. Wastewater treatment plants (WWTPs) are considered to be the main contributors to contamination as they ineffectively eliminate these compounds from wastewater. Simultaneously, they produce solid waste, sludge, which often contains a variety of retained pollutants, including pharmaceuticals. Since sewage sludge is frequently applied to agricultural soil due to its rich nutrient content, pollutants are introduced into the environment in this way. Only a few studies have been carried out on the topic of the analysis of pharmaceuticals in sludge. Therefore, information on the occurrence of pharmaceuticals in sludge is limited. The present study employed quick, easy, cheap, effective, rugged and safe (QuEChERS) extraction and liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) analysis to establish a simple and reliable procedure for determining 16 pharmaceuticals (antibiotics, anticonvulsants, antidepressants and β-blockers) in sewage sludge. The method has been thoroughly validated, and parameters such as linear range, accuracy, precision, matrix effects and detection and quantification limits were assessed. Our method achieved low limits of quantification (0.5–9.0 µg kg−1) and satisfactory recoveries (51–101%). Forty sludge samples from different WWTPs across the Czech Republic were analysed. Fourteen compounds were detected and quantified in most samples, with antidepressants having the highest detection frequency and overall content. Sertraline, with a mean concentration of 521.0 µg kg−1, was notably prevalent alongside its metabolite norsertraline (mean concentration 204.9 µg kg−1). The antibiotic azithromycin was also found at higher levels (mean concentration 185.1 µg kg−1).

Impact of LC-MS/MS quantification methods on analytical results by example of nationwide U.S. environmental samples

Although different quantification methods are extensively used in environmental chemistry, the impact of the choice of method on the quality and range of analytical results is understudied. This two-part study consists of (a) in-lab evaluation and (b) a traditional meta-analysis (n = 66) of commonly used quantification methods): (i) external calibration; (ii) isotope dilution method with authentic target analogs; (iii) isotope dilution with non-target standards; and (iv) standard addition prior to LC-MS/MS in liquid chromatography tandem mass spectrometry (LC-MS/MS) by example of antibiotics in sewage sludge from across the U.S. Using method (i) as the benchmark quantification method for the antibiotic erythromycin in biosolids, other quantification methods resulted in an overestimation (110–450 %) or an underestimation (10–60 %). Using the method (iv) as the benchmark for other compounds resulted in an overestimation (101–14,700 %) or an underestimation (6–98 %). Matrix effects were also observed and were dependent on the matrix and analyte type. For example, in the case of erythromycin, all sample matrices showed signal suppression. This study showed that in the absence of isotopically labeled analogs, the most accurate alternate quantification method may need to be experimentally determined depending on the analyte. Analysis of published literature on pharmaceuticals in sewage sludge indicated that isotope dilution with authentic target analog is most commonly used, followed by non-target isotope standards, standard addition, and finally external calibration.

Simultaneous determination of fourteen pharmaceuticals in sewage sludge using online solid-phase extraction-liquid chromatography-tandem mass spectrometry combined with accelerated solvent extraction.

An online solid-phase extraction (SPE) liquid chromatography tandem mass spectrometry method (HPLC-MS/MS) combined with accelerated solvent extraction (ASE) was developed for simultaneous determination of 14 pharmaceuticals in sludge. In the online SPE procedures, ultrapure water with no additives was used as the loading solvent. In addition, low molecular weight targets such as atenolol were difficult to retain on SPE column after acetone was added to the washing solvent. The response signal of analytes can be greatly improved by adding 0.2% formic acid to the mobile phase. Under the optimized conditions, the recoveries of all the analytes ranged between 75.1 and 112%. Moreover, the limit of detections ranged from 1.8 to 7.9 ug/kg. The precision of analytical data was determined with relative standard deviation (RSD) ≤ 4.87%. This method was successfully applied to determine the concentration of pharmaceuticals in sludge.

From Sewage Sludge to the Soil-Transfer of Pharmaceuticals: A Review.

Sewage sludge, produced in the process of wastewater treatment and managed for agriculture, poses the risk of disseminating all the pollutants contained in it. It is tested for heavy metals or parasites, but the concentration of pharmaceuticals in the sludge is not controlled. The presence of these micropollutants in sludge is proven and there is no doubt about their negative impact on the environment. The fate of these micropollutants in the soil is a new and important issue that needs to be known to finally assess the safety of the agricultural use of sewage sludge. The article will discuss issues related to the presence of pharmaceuticals in sewage sludge and their physicochemical properties. The changes that pharmaceuticals undergo have a significant impact on living organisms. This is important for the implementation of a circular economy, which fits perfectly into the agricultural use of stabilized sewage sludge. Research should be undertaken that clearly shows that there is no risk from pharmaceuticals or vice versa: they contribute to the strict definition of maximum allowable concentrations in sludge, which will become an additional criterion in the legislation on municipal sewage sludge.

Determination of pharmaceuticals and metabolites in sludge and hydrochar after hydrothermal carbonization using sonication-QuEChERS extraction method and UHPLC LTQ/Orbitrap MS.

Pharmaceuticals (PhACs) are an important group of emerging contaminants that are released continuously in the environment from wastewater treatments plants (WWTPs). They can produce biological effects even though at very low concentrations. Conventional WWTPs are not able to remove or degrade completely emerging pollutants resulting in the presence of PhACs in sewage sludge after wastewater treatment. PhACs are found in sludge at low ppb-ppt levels, and their analysis and detection is a difficult task due to the complexity of sewage sludge matrices. Hydrothermal carbonization is currently being proposed as a suitable conversion technology for sewage sludge management to recover valuable products and to be used for soil amendment. In this work, a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS)-based methodology with a dispersive solid-phase extraction (d-SPE) clean-up followed by ultra-high-performance liquid chromatography coupled with high-resolution linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ/Orbitrap MS), operated in positive ionization mode, was adopted to investigate 33 multiclass pharmaceuticals in sewage sludge and in hydrochar produced after hydrothermal carbonization. The analytical method was first optimized studying various extraction parameters and finally validated in terms of linearity, recovery, intra and inter-day precisions, expanded uncertainty (%U)/Horrat ratio at three spiking levels, matrix-effects (ME), process efficiency (PE), and limits of detection and quantification. The developed methodology fulfilled all analytical requirements and was finally applied to sludge samples from the WWTP of Ioannina city where a group of antibiotics was detected at concentrations up to 15ngg-1 and psychiatric drugs such as amisulpride, clozapine, and citalopram were detected at higher concentration levels up to 205, 87.4 and 63.2ngg-1, respectively. The method was also applied to hydrothermally treated sludge sample under different reaction conditions. Most of the antibiotic compounds were not detected, and several psychiatric drugs such as mirtazapine, bupropion, valsartan, diazepam, and caffeine were found at concentrations below the LOQ.

Comparison of ultrasound-assisted extraction, QuEChERS and selective pressurized liquid extraction for the determination of metabolites of parabens and pharmaceuticals in sludge

Analytical methods for the determination of parabens and pharmaceuticals in sludge are scarce and focused on the parent compounds in spite that metabolites can be more toxic and concentrated. This fact is of special relevance when sewage sludge is applied as soil fertiliser what is a common practise in many European countries. In that way, they could affect soils and plants and could even enter into the food chain. In this work, to cover the lack of methodologies for the determination of metabolites of parabens and pharmaceuticals in sludge, two analytical methods have been developed. Proposed analytical methods are based on low-cost and easy-to-perform techniques (ultrasonic-assisted extraction (UAE) and QuEChERS) to make them affordable for routinely control laboratories. The methods have been optimised and validated for the determination of 12 relevant metabolites of parabens and pharmaceuticals and their 7 parent compounds. Proposed methods have been compared with a previously reported method based on selective pressurised liquid extraction (SPLE). UAE method provided higher recoveries, lower MQL, higher precision and higher accuracy than QuEChERS method. Nevertheless, both QuEChERS and UAE methods, in spite of being more time-consuming and difficult to automatise, have been demonstrated to be suitable low-cost alternatives to SPLE. To the best of our knowledge, UAE, QuEChERS and SPLE proposed methods constitute the first multiresidue methods for the simultaneous determination of metabolites of parabens and pharmaceuticals in sewage sludge.

Pharmaceutical load in sewage sludge and biochar produced by hydrothermal carbonization

We investigated the removal of twelve pharmaceuticals in sewage sludge by hydrothermal carbonization (HTC), which has emerged as a technology for improving the quality of organic waste materials producing a valuable biochar material.In this study, the HTC converted sewage sludge samples to a biochar product within 4h at a temperature of 210°C and a resulting pressure of about 15bar. Initial pharmaceutical load of the sewage sludge was investigated as well as the residual concentrations in biochar produced from spiked and eight native sewage sludge samples from three waste water treatment plants. Additionally, the solid contents of source material and product were compared, which showed a considerable increase of the solid content after filtration by HTC.All pharmaceuticals except sulfamethoxazole, which remained below the limit of quantification, frequently occurred in the investigated sewage sludges in the μg/kg dry matter (DM) range. Diclofenac, carbamazepine, metoprolol and propranolol were detected in all sludge samples with a maximum concentration of 800μg/kgDM for metoprolol. HTC was investigated regarding its contaminant removal efficiency using spiked sewage sludge. Pharmaceutical concentrations were reduced for seven compounds by 39% (metoprolol) to≥97% (carbamazepine). In native biochar samples the four compounds phenazone, carbamazepine, metoprolol and propranolol were detected, which confirmed that the HTC process can reduce the load of micropollutants. In contrast to the other investigated compounds phenazone concentration increased, which was further addressed in thermal behaviour studies including three structurally similar potential precursors.

A solid-phase extraction method for rapidly determining the adsorption coefficient of pharmaceuticals in sewage sludge

The partitioning of pharmaceuticals in the environment can be assessed by measuring their adsorption coefficients (Kd) between aqueous and solid phases. Measuring this coefficient in sewage sludge gives an indication of their partitioning behaviour in a wastewater treatment plant and hence contributes to an understanding of their subsequent fate. The regulatory approved method for measuring Kd in sewage sludge is the US Environmental Protection Agency's Office of Prevention, Pesticides and Toxic Substances (OPPTS) guideline 835.1110, which is labour intensive and time consuming. We describe an alternative method for measuring the Kd of pharmaceuticals in sewage sludge using a modified solid-phase extraction (SPE) technique. SPE cartridges were packed at different sludge/PTFE ratios (0.4, 6.0, 24.0 and 40.0% w/w sludge) and eluted with phosphate buffer at pH 7.4. The approach was tested initially using three pharmaceuticals (clofibric acid, diclofenac and oxytetracycline) that covered a range of Kd values. Subsequently, the sorption behaviour of ten further pharmaceuticals with varying physico-chemical properties was evaluated. Results from the SPE method were comparable to those of the OPPTS test, with a correlation coefficient of 0.93 between the two approaches. SPE cartridges packed with sludge and PTFE were stable for up to one year; use within one month reduced variability in measurements (to a maximum of 0.6 log units). The SPE method is low-cost, easy to use and enables the rapid measurement of Kd values for a large number of chemicals. It can be used as an alternative to the more laborious full OPPTS test in environmental fate studies and risk assessments.

Determination of pharmaceuticals in sewage sludge and biochar from hydrothermal carbonization using different quantification approaches and matrix effect studies.

Producing valuable biochar from waste materials using thermal processes like hydrothermal carbonization (HTC) has gained attention in recent years. However, the fate of micropollutants present in these waste sources have been neglected, although they might entail the risk of environmental pollution. Thus, an HPLC-MS/MS method was developed for 12 pharmaceuticals to determine the micropollutant load of biochar, which was made from sewage sludge via HTC within 4 h at 210 °C. Pressurized liquid extraction was applied to extract the compounds. Because of the high load of co-extracted matter, matrix effects in HPLC-MS/MS were investigated using matrix effect profiles. Interfering compounds suppressed 50% of the phenazone signal in sewage sludge and 70% in biochar, for example. The quantification approaches external calibration, internal standard analysis, and standard addition were compared considering recovery rates, standard deviations, and measurement uncertainties. The external analysis resulted in decreased or enhanced recovery rates. Spiking before LC-MS/MS compensated instrumental matrix effects. Still, recovery rates remained below 70% for most compounds because this approach neglects sample losses during the extraction. Internal standards compensated for the matrix effects sufficiently for up to five compounds. The standard addition over the whole procedure proved to compensate for the matrix effects for 11 compounds and achieved recovery rates between 85 and 125%. Additionally, results showed good reproducibility and validity. Only sulfamethoxazole recovery rate remained below 70% in sewage sludge. Real sample analysis showed that three pharmaceuticals were detected in the biochar, while the corresponding sewage sludge source contained 8 of the investigated compounds.

Fluoroquinolones and sulfonamides in sewage sludge compost and their uptake from soil into food plants

Sewage sludge compost can be a source of nutrients for plants and contamination by pharmaceutical products. In this study the presence of some widely used pharmaceuticals in sewage sludge and its compost –namely ciprofloxacin C17H18FN3O3, ofloxacin C18H20FN3O4, norfloxacin C16H18FN3O3, sulfadimethoxine C12H14N4O4S and sulfamethoxazole C10H11N3O3S – was shown. In several sewage sludge samples their concentrations exceeded the relevant trigger values for manure. The highest concentrations of ciprofloxacin, ofloxacin and norfloxacin in the compost ready for commercialization sufficiently exceeded the threshold concentration – 1 μg/kg – for pharmaceuticals in soil. The values of the highest detected concentrations of these pharmaceuticals in compost were respectively 70, 64 and 8 μg/kg. The uptake of these pharmaceuticals was demonstrated from both sandy and loamy soils into food plants such as carrot (Daucus carota L), potato (Solanum tuberosum L) and wheat (Triticum vulgare L). Key words: Soil pollution, plant uptake, pharmaceuticals.

Determination of sorption of seventy-five pharmaceuticals in sewage sludge

Sorption of 75 active pharmaceutical ingredients (APIs) to three different types of sludge (primary sludge, secondary sludge with short and long sludge age respectively) were investigated. To obtain the sorption isotherms batch studies with the APIs mixture were performed in four nominal concentrations to water containing 1 g of sludge. The range of APIs concentrations was between ng L−1 to μg L−1 which are found in the wastewater effluents. Isotherms were obtained for approximately 45 of the APIs, providing distribution coefficients for linear (Kd), Freundlich (Kf) and Langmuir (KL) isotherms. Kd, Kf and KL ranging between 7.1 × 104 and 3.8 × 107, 1.1 × 10−2 and 6.1 × 104 and 9.2 × 10−3 and 1.1 L kg−1, respectively. The obtained coefficients were applied to estimate the fraction of APIs in the water phase (see Abstract Graphic). For 37 of the 75 APIs, the predicted presence in the liquid phase was estimated to >80%. 24 APIs were estimated to be present in the liquid phase between 20 and 80%, and 14 APIs were found to have <20% presence in the liquid phase, i.e. high affinity towards sludge. Furthermore, the effect of pH at values 6, 7 and 8 was evaluated using one way ANOVA-test. A significant difference in Kds due to pH changes were found for 6 of the APIs (variation 10–20%).

Presence of fluoroquinolones and sulfonamides in urban sewage sludge and their degradation as a result of composting

The concentrations of some widely used pharmaceuticals, namely fluoroquinolones (ciprofloxacin C17 H18FN3O3, norfloxacin C17 H18FN3O3 and ofloxacin C18 H20FN3O4 and sulfonamides (sulfadimethoxine C12 H14N4O4s and sulfamethoxazole C10 H11N3O3S were determined in urban sewage sludge utilized for making compost. The levels of degradation of these pharmaceuticals resulting from sludge treatment were assessed. The concentrations of the studied pharmaceuticals sufficiently varied both in sewage sludge and in compost and due to this phenomenon the possible danger resulting from the presence of pharmaceuticals in sewage sludge, used for composting, can not be ignored. The concentrations of the studied pharmaceuticals were lower in compost, if compared to the relevant concentrations in sewage sludge. The highest pharmaceutical concentration in sewage sludge — 426 μg/kg — was detected in the case of ciprofloxacin. The highest concentrations present in compost were 22 μg/kg of norfloxacin and 20 μg/kg of ciprofloxacin. Results show that before using the sewage sludge for making compost or before using the compost a fertilizer for food plants, they should be carefully tested against the content of commonly used pharmaceuticals.

Determination of pharmaceuticals in sewage sludge by pressurized liquid extraction (PLE) coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS)

In this study, we aimed at optimizing a sensitive and reliable method for a simultaneous determination of 31 pharmaceuticals belonging to predominant therapeutic classes identified in different types of sewage sludge proceeding from conventional and advanced wastewater treatment. Freeze-dried sewage sludge was extracted by pressurized liquid extraction technique using accelerated solvent extractor Dionex 300. In order to minimize interferences with matrix components and to preconcentrate target analytes, solid phase extraction was introduced in the method as a clean-up step. The entire method was validated for linearity, precision, accuracy, and method detection limits (MDLs). The method turned out to be specific, sensitive, and reliable for the analysis of sludge of different composition, type, and retention time in the process. The developed sample preparation protocol and previously published method for LC-MS/MS analysis (Gros et al., Talanta 70:678-690, 2006) were successfully applied to monitor the target pharmaceuticals in different types of sewage sludge, i.e., primary sludge, secondary sludge, treated sludge, and sludge proceeding from pilot-scale membrane bioreactors (MBRs) operating in parallel to the conventional activated sludge treatment. Among the investigated pharmaceuticals, 20 were detected in the sludge proceeding from full-scale installations, whereas the MBR sludge concentrations were below MDLs for several compounds. The highest concentrations were recorded for treated and primary sludge. For example, the mean concentration of ibuprofen in the digested sludge was 299.3 +/- 70.9 ng g(-1) dw, whereas in the primary sludge, it was enriched up to 741.1 ng g(-1) dw. Other pharmaceuticals detected at relatively high concentrations were diclofenac, erythromycin, glibenclamide, ketoprofen, ofloxacin, azithromycin (up to 380.7, 164.2, 190.7, 336.3, 454.7, 299.6 ng g(-1) dw in the primary sludge, respectively), gemfibrozil, loratidine, and fluoxetine (up to 189.1, 189.7 and 174.1 ng g(-1) dw in the treated sludge, respectively).

Selective extraction of sulfonamides, macrolides and other pharmaceuticals from sewage sludge by pressurized liquid extraction

A method for the quantitative determination of three macrolides, five sulfonamides, ranitidine, omeprazole and trimethoprim in sewage sludge samples was developed by using pressurized liquid extraction and high-performance liquid chromatography—electrospray ionization mass spectrometry. The extraction solvent and such operational parameters as temperature, pressure, extraction time and purge time were optimized in pressurized liquid extraction. The experimental conditions were: an extraction solvent of water (pH 3):methanol (1:1, v/v), a temperature of 80 °C, a pressure of 1500 psi, a sample weight of 5 g, an extraction time of 5 min, one cycle, a flush volume of 60% and a purge time of 120 s. All recoveries were over 74%, except those for ranitidine whose value was 54%. The repeatability and reproducibility between days expressed as relative standard deviation ( n = 3) were lower than 11% and 15%, respectively. The limit of detection values ranged from 2 to 11 μg/kg dry weight (d.w.). The method was applied to determine the pharmaceuticals in sewage sludge from two domestic sewage treatment plants. Roxithromycin and tylosin were determined in the samples and tylosin showed the highest value (4.0 mg/kg d.w.).

Pressurized liquid extraction of pharmaceuticals from sewage‐sludge

A method for the quantitative determination of ten pharmaceuticals in sewage sludge was developed by using pressurized liquid extraction (PLE) and HPLC-MS with ESI (HPLC-(ESI)MS). The PLE was optimized with regard to solvents and operational parameters, such as temperature, pressure, extraction time, and purge time. The optimum conditions were: 50 mM phosphoric acid/methanol (1:1 v/v) as the extraction solvent, temperature of 100 degrees C, pressure of 100 bar, extraction time 15 min, 2 cycles, flush volume 150% and purge time 300 s. All recoveries for pharmaceuticals were over 68% except for salicylic acid. The repetitivity and reproducibility between days expressed as RSD was lower than 8% for repetitivity and 10% for reproducibility. The LOD of all compounds was lower than 10 microg/kg of dry weight of sewage sludge. The method was applied to determine the pharmaceuticals in sewage sludge from two domestic sewage treatment plants (STPs). The samples were collected every three months between February 2004 and June 2005. Some pharmaceuticals were determined in the samples and naproxen showed the highest value (242 microg/kg of dry weight).

Pharmaceuticals and personal care products in biosolids/sewage sludge: the interface between analytical chemistry and regulation

Modern sanitary practices result in large volumes of human waste, as well as domestic and industrial sewage, being collected and treated at common collection points, wastewater treatment plants (WWTPs). In recognition of the growing use of sewage sludge as fertilizers and soil amendments, and the scarcity of current data regarding the chemical constituents in sewage sludge, the US National Research Council (NRC) in 2002 produced a report on sewage sludge. Among the NRC's recommendations was the need for investigating the occurrence of pharmaceuticals and personal care products (PPCPs) in sewage sludge. PPCPs are a diverse array of non-regulated contaminants that had not been studied in previous sewage sludge surveys but which are likely to be present. The focus of this paper will be to review the current analytical methodologies available for investigating whether pharmaceuticals are present in WWTP-produced sewage sludge, to summarize current regulatory practices regarding sewage sludge, and to report on the presence of pharmaceuticals in sewage sludge.