| 1. |
- Been, Frederic, et al.
(författare)
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Risk-based prioritization of suspects detected in riverine water using complementary chromatographic techniques
- 2021
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Ingår i: Water Research. - : Elsevier BV. - 0043-1354 .- 1879-2448. ; 204
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Tidskriftsartikel (refereegranskat)abstract
- Surface waters are widely used as drinking water sources and hence their quality needs to be continuously monitored. However, current routine monitoring programs are not comprehensive as they generally cover only a limited number of known pollutants and emerging contaminants. This study presents a risk-based approach combining suspect and non-target screening (NTS) to help extend the coverage of current monitoring schemes. In particular, the coverage of NTS was widened by combining three complementary separations modes: Reverse phase (RP), Hydrophilic interaction liquid chromatography (HILIC) and Mixed-mode chromatography (MMC). Suspect lists used were compiled from databases of relevant substances of very high concern (e.g., SVHCs) and the concentration of detected suspects was evaluated based on ionization efficiency prediction. Results show that suspect candidates can be prioritized based on their potential risk (i.e., hazard and exposure) by combining ionization efficiency-based concentration estimation, in vitro toxicity data or, if not available, structural alerts and QSAR.based toxicity predictions. The acquired information shows that NTS analyses have the potential to complement target analyses, allowing to update and adapt current monitoring programs, ultimately leading to improved monitoring of drinking water sources.
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| 2. |
- Bieber, Stefan, et al.
(författare)
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Electrospray Ionization Efficiency Predictions and Analytical Standard Free Quantification for SFC/ESI/HRMS
- 2023
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Ingår i: Journal of the American Society for Mass Spectrometry. - 1044-0305 .- 1879-1123. ; 34:7, s. 1511-1518
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Tidskriftsartikel (refereegranskat)abstract
- Supercritical fluid chromatography (SFC) is a promising, sustainable, and complementary alternative to liquid chromatography (LC) and has often been coupled with high resolution mass spectrometry (HRMS) for nontarget screening (NTS). Recent developments in predicting the ionization efficiency for LC/ESI/HRMS have enabled quantification of chemicals detected in NTS even if the analytical standards of the detected and tentatively identified chemicals are unavailable. This poses the question of whether analytical standard free quantification can also be applied in SFC/ES/HRMS. We evaluate both the possibility to transfer an ionization efficiency predictions model, previously trained on LC/ESI/HRMS data, to SFC/ESI/HRMS as well as training a new predictive model on SFC/ESI/HRMS data for 127 chemicals. The response factors of these chemicals ranged over 4 orders of magnitude in spite of a postcolumn makeup flow, expectedly enhancing the ionization of the analytes. The ionization efficiency values were predicted based on a random forest regression model from PaDEL descriptors and predicted values showed statistically significant correlation with the measured response factors (p < 0.05) with Spearman’s rho of 0.584 and 0.669 for SFC and LC data, respectively. Moreover, the most significant descriptors showed similarities independent of the chromatography used for collecting the training data. We also investigated the possibility to quantify the detected chemicals based on predicted ionization efficiency values. The model trained on SFC data showed very high prediction accuracy with median prediction error of 2.20×, while the model pretrained on LC/ESI/HRMS data yielded median prediction error of 5.11×. This is expected, as the training and test data for SFC/ESI/HRMS have been collected on the same instrument with the same chromatography. Still, the correlation observed between response factors measured with SFC/ESI/HRMS and predicted with a model trained on LC data hints that more abundant LC/ESI/HRMS data prove useful in understanding and predicting the ionization behavior in SFC/ESI/HRMS.
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| 3. |
- Costalunga, Riccardo, et al.
(författare)
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Sodium adduct formation with graph-based machine learning can aid structural elucidation in non-targeted LC/ESI/HRMS
- 2022
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Ingår i: Analytica Chimica Acta. - : Elsevier BV. - 0003-2670 .- 1873-4324. ; 1204
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Tidskriftsartikel (refereegranskat)abstract
- Non-targeted screening with LC/ESI/HRMS aims to identify the structure of the detected compounds using their retention time, exact mass, and fragmentation pattern. Challenges remain in differentiating between isomeric compounds. One untapped possibility to facilitate identification of isomers relies on different ionic species formed in electrospray. In positive ESI mode, both protonated molecules and adducts can be formed; however, not all isomeric structures form the same ionic species. The complicated mechanism of adduct formation has hindered the use of this molecular characteristic in the structural elucidation in non-targeted screening. Here, we have studied the adduct formation for 94 small molecules with ion mobility spectra and compared collision cross-sections of the respective ions. Based on the results we developed a fast support vector machine classifier with polynomial kernels for accurately predicting the sodium adduct formation in ESI/HRMS. The model is trained on five independent data sets from different laboratories and uses the graph-based connectivity of functional groups and PubChem fingerprints to predict the sodium adduct formation in ESI/HRMS. The validation of the model showed an accuracy of 74.7% (balanced accuracy 70.0%) on a dataset from an independent laboratory, which was not used in the training of the model. Lastly, we applied the classification algorithm to the SusDat database by NORMAN network to evaluate the proportion of isomeric compounds that could be distinguished based on predicted sodium adduct formation. It was observed that sodium adduct formation probability can provide additional selectivity for about one quarter of the exact masses and, therefore, shows practical utility for structural assignment in non-targeted screening.
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| 4. |
- Dulio, Valeria, et al.
(författare)
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The NORMAN Association and the European Partnership for Chemicals Risk Assessment (PARC) : let’s cooperate!
- 2020
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Ingår i: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 32:1
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Tidskriftsartikel (refereegranskat)abstract
- The Partnership for Chemicals Risk Assessment (PARC) is currently under development as a joint research and innovation programme to strengthen the scientific basis for chemical risk assessment in the EU. The plan is to bring chemical risk assessors and managers together with scientists to accelerate method development and the production of necessary data and knowledge, and to facilitate the transition to next-generation evidence-based risk assessment, a non-toxic environment and the European Green Deal. The NORMAN Network is an independent, well-established and competent network of more than 80 organisations in the field of emerging substances and has enormous potential to contribute to the implementation of the PARC partnership. NORMAN stands ready to provide expert advice to PARC, drawing on its long experience in the development, harmonisation and testing of advanced tools in relation to chemicals of emerging concern and in support of a European Early Warning System to unravel the risks of contaminants of emerging concern (CECs) and close the gap between research and innovation and regulatory processes. In this commentary we highlight the tools developed by NORMAN that we consider most relevant to supporting the PARC initiative: (i) joint data space and cutting-edge research tools for risk assessment of contaminants of emerging concern; (ii) collaborative European framework to improve data quality and comparability; (iii) advanced data analysis tools for a European early warning system and (iv) support to national and European chemical risk assessment thanks to harnessing, combining and sharing evidence and expertise on CECs. By combining the extensive knowledge and experience of the NORMAN network with the financial and policy-related strengths of the PARC initiative, a large step towards the goal of a non-toxic environment can be taken.
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| 5. |
- Gornischeff, Artur, et al.
(författare)
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Characterization of wines with liquid chromatography electrospray ionization mass spectrometry : Quantification of amino acids via ionization efficiency values
- 2020
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1620
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Tidskriftsartikel (refereegranskat)abstract
- Quantification of analysis results for the suspect and non-targeted screening is essential for obtaining meaningful insight from the measurements. Ionization efficiency predictions is a possible approach to enable quantitation without standard substances. This is, however, especially challenging for the analysis carried out by combining the full scan mode either with fragmentation experiments in data-dependent or data-independent acquisition mode. Here we investigate the correlation of ionization efficiency values measured in full scan mode with the response factors measured in multiple reaction monitoring (MRM) mode for derivatized amino acids. We observe good correlation (R-2 of 0.80) for 6-Aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatized amino acids. This encourages the use of the measured ionization efficiency values to estimate amino acid concentrations in different beverages. We apply the measured ionization efficiency values for estimating the concentration of amino acids for measurements done both in full scan as well as in MRM mode in wines and beers. We show that the calculated concentrations are in very good correlation with measured values (R-2 of 0.71 to 1.00). The method possesses average trueness of 70.5% and shows an insignificant matrix effect.
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| 6. |
- Groff II, Louis C., et al.
(författare)
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Uncertainty estimation strategies for quantitative non-targeted analysis
- 2022
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 414:17, s. 4919-4933
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Tidskriftsartikel (refereegranskat)abstract
- Non-targeted analysis (NTA) methods are widely used for chemical discovery but seldom employed for quantitation due to a lack of robust methods to estimate chemical concentrations with confidence limits. Herein, we present and evaluate new statistical methods for quantitative NTA (qNTA) using high-resolution mass spectrometry (HRMS) data from EPA’s Non-Targeted Analysis Collaborative Trial (ENTACT). Experimental intensities of ENTACT analytes were observed at multiple concentrations using a semi-automated NTA workflow. Chemical concentrations and corresponding confidence limits were first estimated using traditional calibration curves. Two qNTA estimation methods were then implemented using experimental response factor (RF) data (where RF = intensity/concentration). The bounded response factor method used a non-parametric bootstrap procedure to estimate select quantiles of training set RF distributions. Quantile estimates then were applied to test set HRMS intensities to inversely estimate concentrations with confidence limits. The ionization efficiency estimation method restricted the distribution of likely RFs for each analyte using ionization efficiency predictions. Given the intended future use for chemical risk characterization, predicted upper confidence limits (protective values) were compared to known chemical concentrations. Using traditional calibration curves, 95% of upper confidence limits were within ~tenfold of the true concentrations. The error increased to ~60-fold (ESI+) and ~120-fold (ESI−) for the ionization efficiency estimation method and to ~150-fold (ESI+) and ~130-fold (ESI−) for the bounded response factor method. This work demonstrates successful implementation of confidence limit estimation strategies to support qNTA studies and marks a crucial step towards translating NTA data in a risk-based context.
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| 7. |
- Hollender, Juliane, et al.
(författare)
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NORMAN guidance on suspect and non-target screening in environmental monitoring
- 2023
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Ingår i: Environmental Sciences Europe. - : Springer Nature. - 2190-4707 .- 2190-4715. ; 35:1
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Forskningsöversikt (refereegranskat)abstract
- 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.
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| 8. |
- Khabazbashi, Sara, et al.
(författare)
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Estimation of the concentrations of hydroxylated polychlorinated biphenyls in human serum using ionization efficiency prediction for electrospray
- 2022
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 414:25, s. 7451-7460
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxylated PCBs are an important class of metabolites of the widely distributed environmental contaminants polychlorinated biphenyls (PCBs). However, the absence of authentic standards is often a limitation when subject to detection, identification, and quantification. Recently, new strategies to quantify compounds detected with non-targeted LC/ESI/HRMS based on predicted ionization efficiency values have emerged. Here, we evaluate the impact of chemical space coverage and sample matrix on the accuracy of ionization efficiency-based quantification. We show that extending the chemical space of interest is crucial in improving the performance of quantification. Therefore, we extend the ionization efficiency-based quantification approach to hydroxylated PCBs in serum samples with a retraining approach that involves 14 OH-PCBs and validate it with an additional four OH-PCBs. The predicted and measured ionization efficiency values of the OH-PCBs agreed within the mean error of 2.1 × and enabled quantification with the mean error of 4.4 × or better. We observed that the error mostly arose from the ionization efficiency predictions and the impact of matrix effects was of less importance, varying from 37 to 165%. The results show that there is potential for predictive machine learning models for quantification even in very complex matrices such as serum. Further, retraining the already developed models provides a timely and cost-effective solution for extending the chemical space of the application area.
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| 9. |
- Kruve, Anneli, et al.
(författare)
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Benchmarking of the quantification approaches for the non-targeted screening of micropollutants and their transformation products in groundwater
- 2021
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 413:6, s. 1549-1559
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Tidskriftsartikel (refereegranskat)abstract
- A wide range of micropollutants can be monitored with non-targeted screening; however, the quantification of the newly discovered compounds is challenging. Transformation products (TPs) are especially problematic because analytical standards are rarely available. Here, we compared three quantification approaches for non-target compounds that do not require the availability of analytical standards. The comparison is based on a unique set of concentration data for 341 compounds, mainly pesticides, pharmaceuticals, and their TPs in 31 groundwater samples from Switzerland. The best accuracy was observed with the predicted ionization efficiency-based quantification, the mean error of concentration prediction for the groundwater samples was a factor of 1.8, and all of the 74 micropollutants detected in the groundwater were quantified with an error less than a factor of 10. The quantification of TPs with the parent compounds had significantly lower accuracy (mean error of a factor of 3.8) and could only be applied to a fraction of the detected compounds, while the mean performance (mean error of a factor of 3.2) of the closest eluting standard approach was similar to the parent compound approach.
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| 10. |
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