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Distribution of log P and log D (pH 7.4) values of the compounds listed in ESM Table S1 (classification according to application as in Fig. 1b). Details of the correlation between log P and log D (7.4) is shown in Fig. 1c). Contours show estimated log P scopes of the sample preparation and separation techniques as discussed in this article. DLLME, dispersive liquid-liquid microextraction; EC, evaporative concentration; EME,
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Recent years showed a boost in knowledge about the presence and fate of micropollutants in the environment. Instrumental and methodological developments mainly in liquid chromatography coupled to mass spectrometry hold a large share in this success story. These techniques soon complemented gas chromatography and enabled the analysis of more polar c...
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Context 1
... is due to insufficient retention, leading to poor extraction efficiencies and poor separation of early eluting peaks in RPLC. Figure 2 provides an overview on current analytical methods (sample preparation and separation) applicable for vPIC analysis and the range of log P/log D values, which can be covered (in part, however, of course not the whole range with a single analysis). Limitations regarding the polarity range covered are evident in many upto-date reviews [4][5][6][7]. ...
Context 2
... solvents could be miniaturization of the analytical column, which is already a trend in bioanalysis [79]. However, this may be at the cost of a lowered sample loadability and is thus an option for biota but not for water analysis. Overall, we expect HILIC applications to increase as its polarity range almost ideally complements RPLC analysis (see Fig. 2), while the same equipment can be used. Multidimensional applications combining RPLC and HILIC are discussed in Section 2D ...
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Nano-sized ion exchangers (NIEs) combine the properties of common bulk ion-exchange polymers with the unique advantages of downsizing into nanoparticulate matter. In particular, being by nature milti-charged ions exchangers, NIEs possess high reactivity and stability in suspensions. This brief review provides an introduction to the emerging landsca...
Citations
... Therefore, adequate sample treatment procedures are mandatory for their enrichment in a matrixfree solvent [25]. In the case of PMTs, common extraction/clean-up techniques, such as solid phase extraction (SPE) or liquid-liquid extraction (LLE) might fail to achieve the required objective [26]. In that context, alternative SPE sorbents and LLE variations have been tested to extract very polar organic compounds from aqueous samples. ...
Persistent, mobile and toxic substances have drawn attention nowadays due to their particular properties, but they are overlooked in human monitorization works, limiting the knowledge of the human exposome. In that sense, human urine is an interesting matrix since not only parent compounds are eliminated, but also their phase II metabolites that could act as biomarkers. In this work, 11 sample preparation procedures involving preconcentration were tested to ensure maximum analytical coverage in human urine using mixed-mode liquid chromatography coupled with high-resolution tandem mass spectrometry. The optimized procedure consisted of a combination of solid-phase extraction and salt-assisted liquid-liquid extraction and it was employed for suspect screening. Additionally, a non-discriminatory dilute-and-shoot approach was also evaluated. After evaluating the workflow in terms of limits of identification and type II errors (i.e., false negatives), a pooled urine sample was analysed. From a list of 1450 suspects and in-silico simulated 1568 phase II metabolites (i.e. sulphates, glucuronides, and glycines), 44 and 14 substances were annotated, respectively. Most of the screened suspects were diverse industrial chemicals, but biocides, natural products and pharmaceuticals were also detected. Lastly, the complementarity of the sample preparation procedures, columns, and analysis conditions was assessed. As a result, dilute-and-shoot and the Acclaim Trinity P1 column at pH = 3 (positive ionization) and pH = 7 (negative ionization) allowed the maximum coverage since almost 70 % of the total suspects could be screened using those conditions.
... While optimized capillary electrophoresis with diode array detection achieves medium ng/L detection limits, MS remains the preferred method for non-target screenings, especially in research laboratories, owing to fewer restrictions compared to ion chromatography-mass spectrometry hyphenation and its environmentally friendly attributes with low solvent consumption. In discussions and tables, references may be numbered sequentially [121]. ...
In the wake of rapid advancements in the pharmaceutical, food, and agricultural industries, the environment faces an increasing influx of diverse compounds, both intentionally and unintentionally released. These compounds fall into two categories: persistent and emerging pollutants. Persistent pollutants, characterized by their resistance to degradation and potential to accumulate in the environment, pose serious ecological threats. The Water Framework Directive (WFD) plays a pivotal role in monitoring and regulating these substances. This review discusses various contemporary analytical approaches to determine problematic substances, including benzo(a)pyrene, cypermethrin, dichlorvos, heptachlor, and heptachlor epoxide, aligning with the priorities outlined in the 2013 WFD classification. This review focuses on diverse water sampling methods, sample preparation techniques, and analytical methods, encompassing chromatographic, spectroscopic, and electrochemical approaches, with the primary goal of achieving the requirement laid on analytical methods used for the determination of maximum allowable concentrations defined in the WFD. Chromatographic methods, utilizing diverse mass spectrometers, have achieved detection limits as low as 10−6 μg/L, while modern electroanalytical techniques reach levels as low as 10−13 μg/L, reflecting an ongoing collective effort to enhance monitoring and safeguard the health of aquatic ecosystems. From sampling methods, large-volume sampling and passive sampling devices have been shown to be a cost-effective and modern solution, addressing limitations in traditional sampling methods, even if both of them face important pros and cons in terms of quantitative analysis.
... The second challenge is the wide range of polarities of anthropogenic substances discharged to the aquatic ecosystem, enforcing the use of multiple and complex methods to analyze a wide polarity detection range. For instance, separation principles for nonpolar substances, such as hormones and sartans, cannot be applied to polar compounds, such as iodinated X-ray contrast agents [11]. Samples with this broad polarity spectrum can no longer be analyzed by one-dimensional liquid chromatography (1D LC) unless two chromatographic methods with different selectivity are used. ...
... This "matrix effect" typically encompasses disturbances such as background increase, chromatographic alteration (retention time shifts, peak broadening) or ion suppression caused by preferential ionisation of matrix molecules (David et al., 2014, Hajeb et al., 2022, González-Gaya et al., 2021 and is sought minimised through rigorous clean-up steps in target analyses. Efforts are being made to develop generic and non-selective protocols to extract CECs with different physicochemical properties for suspect and non-target screening approaches, offering an acceptable compromise between selectivity and efficiently removing interfering matrix compounds (Dirtu et al., 2012, Fidalgo-Used et al., 2007, Knoll et al., 2020, Dürig et al., 2020, Xia et al., 2019, Baduel et al., 2015, Vitale et al., 2021, Chaker et al., 2022. Furthermore, recently developed guidelines for sampling, sample preparation, chemical analysis and data analysis will likely contribute to more harmonisation in this rapidly developing field (Caballero-Casero et al., 2021b). ...
A collaborative trial involving 16 participants from nine European countries was conducted within the NORMAN network in efforts to harmonise suspect and non-target screening of environmental contaminants in whole fish samples of bream (Abramis brama). Participants were provided with freeze-dried, homogenised fish samples from a contaminated and a reference site, extracts (spiked and non-spiked) and reference sample preparation protocols for liquid chromatography (LC) and gas chromatography (GC) coupled to high resolution mass spectrometry (HRMS). Participants extracted fish samples using their in-house sample preparation method and/or the protocol provided. Participants correctly identified 9–69 % of spiked compounds using LC-HRMS and 20–60 % of spiked compounds using GC-HRMS. From the contaminated site, suspect screening with participants’ own suspect lists led to putative identification of on average ∼145 and ∼20 unique features per participant using LC-HRMS and GC-HRMS, respectively, while non-target screening identified on average ∼42 and ∼56 unique features per participant using LC-HRMS and GC-HRMS, respectively. Within the same sub-group of sample preparation method, only a few features were identified by at least two participants in suspect screening (16 features using LC-HRMS, 0 features using GC-HRMS) and non-target screening (0 features using LC-HRMS, 2 features using GC-HRMS). The compounds identified had log octanol/water partition coefficient (KOW) values from −9.9 to 16 and mass-to-charge ratios (m/z) of 68 to 761 (LC-HRMS and GC-HRMS). A significant linear trend was found between log KOW and m/z for the GC-HRMS data. Overall, these findings indicate that differences in screening results are mainly due to the data analysis workflows used by different participants. Further work is needed to harmonise the results obtained when applying suspect and non-target screening approaches to environmental biota samples.
... Highly hydrophilic compounds (in terms of environmental concern often referred to as persistent mobile organic chemicals, PMOC) [109] are often not retained on typical RP columns and elute at or close to the column dead time, where typically strong ion suppression and interferences are observed, impeding reliable peak detection, identification and quantification. Several approaches are available to achieve a separation of highly hydrophilic, neutral and ionic compounds [110,111], including HILIC, SFC, capillary electrophoresis, ion chromatography (IC) and MMLC. Typically, the logK OW (or logD OW in case of ionisable compounds) is used as an approximation to assess mobility and also chromatographic behaviour, although the LC retention of compounds is more complex and logD OW alone is insufficient to predict whether a compound is actually retained on a RPLC column or not [112]. ...
... Capillary electrophoresis and ion chromatography have so far been mainly used for the analysis of inorganic ions, but allow also a separation of ionic organic compounds with a wide polarity range. However, both techniques require a specific interfacing when coupled to MS and have some methodological restrictions, which so far limited a more widespread application in environmental analysis [111,112], although quite a few studies employed capillary electrophoresis in non-targeted metabolomics [113]. Various types of capillary electrophoresis separations exist, of which capillary zone electrophoresis (CZE), micellar electrokinetic capillary chromatography (MEKC) and capillary electrochromatography (CEC) are most widely used [114]. ...
Increasing production and use of chemicals and awareness of their impact on ecosystems and humans has led to large interest for broadening the knowledge on the chemical status of the environment and human health by suspect and non-target screening (NTS). To facilitate effective implementation of NTS in scientific, commercial and governmental laboratories, as well as acceptance by managers, regulators and risk assessors, more harmonisation in NTS is required. To address this, NORMAN Association members involved in NTS activities have prepared this guidance document, based on the current state of knowledge. The document is intended to provide guidance on performing high quality NTS studies and data interpretation while increasing awareness of the promise but also pitfalls and challenges associated with these techniques. Guidance is provided for all steps; from sampling and sample preparation to analysis by chromatography (liquid and gas—LC and GC) coupled via various ionisation techniques to high-resolution tandem mass spectrometry (HRMS/MS), through to data evaluation and reporting in the context of NTS. Although most experience within the NORMAN network still involves water analysis of polar compounds using LC–HRMS/MS, other matrices (sediment, soil, biota, dust, air) and instrumentation (GC, ion mobility) are covered, reflecting the rapid development and extension of the field. Due to the ongoing developments, the different questions addressed with NTS and manifold techniques in use, NORMAN members feel that no standard operation process can be provided at this stage. However, appropriate analytical methods, data processing techniques and databases commonly compiled in NTS workflows are introduced, their limitations are discussed and recommendations for different cases are provided. Proper quality assurance, quantification without reference standards and reporting results with clear confidence of identification assignment complete the guidance together with a glossary of definitions. The NORMAN community greatly supports the sharing of experiences and data via open science and hopes that this guideline supports this effort.
... In the analytical chemistry field, effort s have been made in developing methods to analyse chemicals in human matrices, such as urine [ 4 , 5 ], plasma [ 6 , 7 ], or breast milk [ 8 , 9 ]. In many of those works, only semi-polar or non-polar chemicals are monitored when it comes to organic compounds, while very polar compounds are overlooked, as happens in most environmental studies [10] . ...
... At present, an analytical gap exists for the analysis of PMOCs, which makes the study of their occurrence, fate, or potential adverse effects, and, therefore, their subsequent integration into regulatory lists challenging [10] . In that scenario, The German Environment Agency (UBA) proposed over several years criteria for identifying PMT or vPvMT substances in the regulatory context of the EU REACH (registration, evaluation, authorisation, and restriction of chemicals), for instance [15] . ...
... Regarding sample treatment, the extraction of PMOCs from aqueous samples is demanding and common extraction and/or clean-up techniques, such as solid phase extraction (SPE) or liquidliquid extraction (LLE) usually fail to achieve the required objective [10] . In that context, lyophilization and reconstitution of the sample [ 16 , 17 ] or even "dilute-and-shoot" (DS) approaches with direct injection [ 18 , 19 ] have been tested for minimizing losses in sample preparation. ...
In this work, a comprehensive method for the simultaneous determination of 33 diverse persistent and mobile organic compounds (PMOCs) in human urine was developed by dilute-and-shoot (DS) followed by mixed-mode liquid chromatography coupled with tandem mass spectrometry (MMLC-MS/MS). In the sample preparation step, DS was chosen since it allowed the quantification of all targets in comparison to lyophilization. For the chromatographic separation, Acclaim Trinity P1 and P2 trimodal columns provided greater capacity for retaining PMOCs than reverse phase and hydrophilic interaction liquid chromatography. Therefore, DS was validated at 5 and 50 ng/mL in urine with both mixed mode columns at pH = 3 and 7. Regarding figures of merit, linear calibration curves (r2 > 0.999) built between instrumental quantification limits (mostly below 5 ng/mL) and 500 ng/mL were achieved. Despite only 60% of the targets were recovered at 5 ng/mL because of the dilution, all PMOCs were quantified at 50 ng/mL. Using surrogate correction, apparent recoveries in the 70-130% range were obtained for 91% of the targets. To analyse human urine samples, the Acclaim Trinity P1 column at pH = 3 and 7 was selected as a consensus between analytical coverage (i.e. 94% of the targets) and chromatographic runs. In a pooled urine sample, industrial chemicals (acrylamide and bisphenol S), biocides and their metabolites (2-methyl-4-isothiazolin-3-one, dimethyl phosphate, 6-chloropyridine-3-carboxylic acid, and ammonium glufosinate) and an artificial sweetener (aspartame) were determined at ng/mL levels. The outcomes of this work showed that humans are also exposed to PMOCs due to their persistence and mobility, and therefore, further human risk assessment is needed.
... In this study, the Oasis HLB cartridges, which are well-known for their versatility in the field of multiresidue analysis of drugs in environmental samples [30][31][32], were applied for the enrichment of the target compounds from aqueous samples as well as for the cleanup of fish extracts. This allowed an efficient (>50%) simultaneous extraction for most of the target compounds, characterized by a wide range of physicochemical properties with log K ow values ranging from − 1.2 to 6.4 and pK a values from 0.7 to 14 (Table S1). ...
In this work, a wide-scope liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative determination of environmental levels of multiclass drugs and their metabolites in water and fish samples was developed. The method allowed the reliable determination of 44 drugs, covering a rather wide range of chemistries and physicochemical characteristics. In order to obtain a reliable and robust analytical protocol, different combinations of extraction and cleanup techniques were systematically examined. Aqueous samples were extracted using a simple Oasis HLB SPE enrichment protocol with pH-optimized sample percolation (pH 3). The extraction of cryo-homogenized biota samples was performed using double extraction with MeOH basified with 0.5% NH3, which allowed high extraction recoveries for all target analytes. The problem of the coextracted lipid matrix, which is known to be the key obstacle for reliable biota analysis, was systematically examined in a series of model cleanup experiments. A combination of cryo-precipitation, filtration, and HLB SPE cleanup was proposed as a protocol, which allowed reliable and robust analysis of all target compounds at low ng/g levels. At the final conditions, the method which was validated at three concentration levels showed high extraction recoveries (68-97%), acceptable matrix effects (12 to -32%), accuracies (81-129%), and reproducibilities (3-32%) for all analytes. The developed method was used to determine drug concentrations in river water and in feral freshwater fish, including whole fish and muscle tissue, from the Sava River (Croatia), in order to estimate their corresponding bioaccumulation potential. With respect to bioaccumulation potential in whole fish and fish muscle, the most relevant drugs were lisinopril, sertraline, terbinafine, torsemide, diazepam, desloratadine, and loratadine with estimated bioaccumulation factors ranging from 20 to 838 and from 1 to 431, respectively.
... Availability of monitoring data regarding their removal in WWTPs is only available for a few well-known chemicals, such as ethylenediaminetetraacetate (EDTA) or 1,4-dioxane (Stepien et al., 2014), benzotriazole Farré et al., 2008) or acesulfame (Scheurer et al., 2009;Rizzo et al., 2019). Multiple preparative and chromatographic techniques, such as hydrophilic interaction chromatography (HILIC), mixed-mode liquid chromatography (MMLC), supercritical fluid chromatography (SFC), capillary electrophoresis (CE) or ion chromatography (IC) (Montes et al., 2017;Höcker et al., 2020;Knoll et al., 2020;Schulze et al., 2020;Zahn et al., 2020) have been used for the analysis of PM-substances, but neither of these methods are extensively used for monitoring or screening purposes hampering the availability of data. ...
Persistent and mobile (PM) substances are able to spread quickly in the water cycle and were thus identified as potentially problematic for the environment and water quality. If also toxic (PMT) or very persistent and very mobile (vPvM) their regulation under REACH as substances of very high concern is foreseen. Yet, knowledge on the effectiveness of advanced wastewater treatment in removing PM-substances from WWTP effluents is limited to few rather well-known chemicals. The occurrence and behavior of 111 suspected and known PM-substances was investigated in two wastewater treatment plants employing either powdered activated carbon (PAC, full-scale) or ozonation with subsequent sand/anthracite filtration (pilot-scale) and an additional granular activated carbon (GAC) filtration was investigated. 72 of the 111 PM-substances analyzed were detected at least once in the secondary effluent of either wastewater treatment plant, resulting in total concentrations of 104 μg/L and 40 μg/L, respectively. While PAC removed 32 % of PM-substances well, the total PM burden in the effluent was only reduced from 103 μg/L to 87 μg/L. Ozonation and the subsequent sand/anthracite filtration was able to reduce the PM burden in wastewater from 40 μg/L to 19 μg/L, showing a higher removal efficacy than PAC in this study. The additional GAC filtration further reduced the total PM-concentration to 13 μg/L. Among the investigated PM-chemicals detected were constituents of ionic liquids: The anion hexafluorophosphate was one of few chemicals that was detected in effluent concentrations >1 μg/L and could not be removed by the processes studied, showing that for some chemicals preventive actions may be required.
... The current status of the analysis of very polar and ionic substances was summarized by Knoll et al. (2020) and Zahn et al. (2020). Major limitations in the analysis of very polar and ionic compounds are the sample preparation and chromatographic separation because such compounds do not retard well on C18 or polymeric materials such as HLB, often used for enrichment and separation in environmental analysis (Zahn et al., 2020). ...
... In IC-MS method development, there are some challenges to overcome (Knoll et al., 2020;Zahn et al., 2020), especially when coupled to mass spectrometry. For anion chromatography, these challenges include the need to eliminate non-volatile mobile phase components such as K + by ion suppressors, matrix effects in electrospray ionization like ion suppression induced by inorganic salt ions (Furey et al., 2013), and reduced ionization efficiency in buffers used for IC elution. ...
Polar, mobile and toxic (PMT), and very polar and very mobile (vPvM) substances pose a threat to the water cycle but are often not covered in conventional environmental monitoring programs. Within this realm of substances, one compound class of concern are pesticides and their transformation products as they are deliberately introduced into the environment. To detect very polar anionic substances, including many pesticide transformation products with log DOW values ranging between -7.4 and 2.2, an ion chromatography high-resolution mass spectrometry method was developed in this study. Since inorganic anions, such as chloride and sulfate, interfere with the analysis of organic species, their removal via precipitation with Ag/Ba/H cartridges was assessed. To improve LOQs, vacuum-assisted evaporative concentration (VEC) was evaluated. By using VEC and removing inorganic salt ions, the median LOQ improved from 100 ng/L in evian® water without sample treatment to 10 ng/L after enrichment and 30 ng/L in karst groundwater. Using this method, twelve out of 64 substances covered by the final method were found in karst groundwater in concentrations of up to 5600 ng/L, and seven exceeded 100 ng/L. To the authors' knowledge, the dimethenamid TP M31 and chlorothalonil TP SYN548008 were detected for the first time in groundwater samples. The coupling to a high-resolution mass spectrometer also allows for non-target screening and hence, this method presents a powerful tool to tackle PMT/vPvM substances.
... Therefore, the CZE method is more economical and environmentally friendly than the HPLC method. Notably, several recent studies reported green analytical CZE methods for a wide range of applications including pharmaceutical, medicinal, food, and environmental analyses [43][44][45][46]. In general, the literature reported that CZE technique provided greener methods than HPLC technique [47]. ...
A capillary zone electrophoretic (CZE) method was developed, validated, and applied for the assay of metformin (MET) and pioglitazone (PIO) in pharmaceutical formulations. The optimum running buffer composition was found to be 75 mmol/L phosphate buffer containing 30% acetonitrile (ACN) at pH 4.0. The optimum instrumental conditions were found to be injection time, 10 s; applied voltage, 25 kV; hydrodynamic injection pressure, 0.5 psi for 10 sec, capillary temperature, 25 °C; and the detection wavelength, 210 nm. The quantifications were calculated based on the ratio of the peak areas of analytes to atenolol as an internal standard. The CZE method was validated in terms of accuracy (98.21–104.81%), intra- and inter-day precision of migration time and peak area (relative standard deviation ≤ 5%), linearity (correlation coefficients ≥ 0.9985), limit of detection (≤ 0.277 μg/mL), and limit of quantitation (≤ 0.315 μg/mL). The proposed method was applied for the analysis of PIO and MET both individually and in a combined dosage tablet formulation. All electrophoretic parameters were calculated and evaluated. A previously reported high-performance liquid chromatographic (HPLC) method was also applied to the same samples. A comprehensive comparison was then carried out for the analytical features of both methods CZE and HPLC. Comparable results were obtained with the advantage of reagent consumption and separation efficiency of CZE over HPLC and shorter analysis time by HPLC compared with CZE.
