An assessment of quality assurance/quality control efforts in high resolution mass spectrometry non-target workflows for analysis of environmental samples

Abstract The application of non-target analysis (NTA), a comprehensive approach to characterize unknown chemicals, including chemicals of emerging concern has seen a steady increase recently. Given the relative novelty of this type of analysis, robust quality assurance and quality control (QA/QC) measures are imperative to ensure quality and consistency of results obtained using different workflows. Due to fundamental differences to established targeted workflows, new or expanded approaches are necessary; for example to minimize the risk of losing potential substances of interest (i.e. false negatives, Type II error). We present an overview of QA/QC techniques for NTA workflows published to date, specifically focusing on the analysis of environmental samples using liquid chromatography coupled to HRMS. From a QA/QC perspective, we discuss methods used for each step of analysis: sample preparation, chromatography, mass spectrometry, and data processing. We then finish with a series of recommendations to improve the quality assurance of NTA workflows.

[1]  Werner Brack,et al.  Method Development for Selective and Nontargeted Identification of Nitro Compounds in Diesel Particulate Matter , 2017 .

[2]  Juliane Hollender,et al.  Untargeted time-pattern analysis of LC-HRMS data to detect spills and compounds with high fluctuation in influent wastewater. , 2019, Journal of hazardous materials.

[3]  Anna Ledin,et al.  Ecotoxicity of carbamazepine and its UV photolysis transformation products. , 2013, The Science of the total environment.

[4]  Thomas Lin,et al.  Suspect Screening of Maternal Serum to Identify New Environmental Chemical Biomonitoring Targets using Liquid Chromatography-Quadrupole Time-Of-Flight Mass Spectrometry , 2017, Journal of Exposure Science and Environmental Epidemiology.

[5]  T. Croley,et al.  Optimized chemical coverage and data quality for non-targeted screening applications using liquid chromatography/high-resolution mass spectrometry. , 2019, Analytica chimica acta.

[6]  Ian D. Wilson,et al.  Guidelines and considerations for the use of system suitability and quality control samples in mass spectrometry assays applied in untargeted clinical metabolomic studies , 2018, Metabolomics : Official journal of the Metabolomic Society.

[7]  Antony J. Williams,et al.  The CompTox Chemistry Dashboard: a community data resource for environmental chemistry , 2017, Journal of Cheminformatics.

[8]  Emma L Schymanski,et al.  Systematic Exploration of Biotransformation Reactions of Amine-Containing Micropollutants in Activated Sludge. , 2016, Environmental science & technology.

[9]  S. Böcker,et al.  Searching molecular structure databases with tandem mass spectra using CSI:FingerID , 2015, Proceedings of the National Academy of Sciences.

[10]  Anna Sobek,et al.  A strategic screening approach to identify transformation products of organic micropollutants formed in natural waters. , 2017, Environmental science. Processes & impacts.

[11]  Rafael Cela,et al.  Screening for Polar Chemicals in Water by Trifunctional Mixed-Mode Liquid Chromatography-High Resolution Mass Spectrometry. , 2017, Environmental science & technology.

[12]  Evan Bolton,et al.  PubChem 2019 update: improved access to chemical data , 2018, Nucleic Acids Res..

[13]  S. Neumann,et al.  PredRet: prediction of retention time by direct mapping between multiple chromatographic systems. , 2015, Analytical chemistry.

[14]  Shuzhao Li,et al.  Detailed Investigation and Comparison of the XCMS and MZmine 2 Chromatogram Construction and Chromatographic Peak Detection Methods for Preprocessing Mass Spectrometry Metabolomics Data. , 2017, Analytical chemistry.

[15]  Tomáš Pluskal,et al.  Highly accurate chemical formula prediction tool utilizing high-resolution mass spectra, MS/MS fragmentation, heuristic rules, and isotope pattern matching. , 2012, Analytical chemistry.

[16]  Torsten C. Schmidt,et al.  Comparison of Software Tools for Liquid Chromatography–High-Resolution Mass Spectrometry Data Processing in Nontarget Screening of Environmental Samples , 2020 .

[17]  B González-Gaya,et al.  Focused ultrasound-based extraction for target analysis and suspect screening of organic xenobiotics in fish muscle. , 2020, The Science of the total environment.

[18]  Malcolm J Reid,et al.  Target and suspect screening of psychoactive substances in sewage-based samples by UHPLC-QTOF. , 2016, Analytica chimica acta.

[19]  Peter F. Stadler,et al.  Exploration of the chemical space and its three historical regimes , 2019, Proceedings of the National Academy of Sciences.

[20]  A Ruth Godfrey,et al.  Accurate mass measurement: Terminology and treatment of data , 2010, Journal of the American Society for Mass Spectrometry.

[21]  Jian-Bo Wan,et al.  Application of two-dimensional chromatography in the analysis of Chinese herbal medicines. , 2014, Journal of chromatography. A.

[22]  John A. McLean,et al.  Ion Mobility-Mass Spectrometry: Time-Dispersive Instrumentation , 2014, Analytical chemistry.

[23]  Ronald A Hites,et al.  Response to "Letter to the Editor: Optimism for Nontarget Analysis in Environmental Chemistry". , 2019, Environmental science & technology.

[24]  Tobias Bader,et al.  Column bleed in the analysis of highly polar substances: an overlooked aspect in HRMS , 2020, Analytical and Bioanalytical Chemistry.

[25]  Damià Barceló,et al.  Advances in liquid chromatography–high-resolution mass spectrometry for quantitative and qualitative environmental analysis , 2015, Analytical and Bioanalytical Chemistry.

[26]  Reza Aalizadeh,et al.  Extended Suspect and Non-Target Strategies to Characterize Emerging Polar Organic Contaminants in Raw Wastewater with LC-HRMS/MS. , 2015, Environmental science & technology.

[27]  R. J. Vreeken,et al.  High-Resolution Mass Spectrometry Quantification: Impact of Differences in Data Processing of Centroid and Continuum Data , 2018, Journal of The American Society for Mass Spectrometry.

[28]  Kamel Mansouri,et al.  A comparison of three liquid chromatography (LC) retention time prediction models. , 2018, Talanta.

[29]  J. Trottier,et al.  Book Review: Mass Spectrometry: Principles and Applications. E. de Hoffman, J. Charette and W. Stroobant. Wiley, Chichester 1996. ISBN 0 471 96697 5 , 1997 .

[30]  Herbert Oberacher,et al.  Suspect and non-targeted screening of chemicals of emerging concern for human biomonitoring, environmental health studies and support to risk assessment: From promises to challenges and harmonisation issues. , 2020, Environment international.

[31]  Joshua J. Coon,et al.  Sub-part-per-million Precursor and Product Mass Accuracy for High-throughput Proteomics on an Electron Transfer Dissociation-enabled Orbitrap Mass Spectrometer* , 2010, Molecular & Cellular Proteomics.

[32]  Michael Witting,et al.  Tandem HILIC‐RP liquid chromatography for increased polarity coverage in food analysis , 2018, Electrophoresis.

[33]  Emma L. Schymanski,et al.  Mass spectral databases for LC/MS- and GC/MS-based metabolomics: state of the field and future prospects , 2016 .

[34]  Fabio Garofolo.  LC‐MS Instrument Calibration , 2004 .

[35]  Johannes P C Vissers,et al.  Scanning Quadrupole Data-Independent Acquisition, Part B: Application to the Analysis of the Calcineurin-Interacting Proteins during Treatment of Aspergillus fumigatus with Azole and Echinocandin Antifungal Drugs. , 2017, Journal of proteome research.

[36]  Beate I. Escher,et al.  Recent advances in environmental risk assessment of transformation products. , 2011, Environmental science & technology.

[37]  B. M. Simonet,et al.  Quality control in qualitative analysis , 2005 .

[38]  Masanori Arita,et al.  Identification of small molecules using accurate mass MS/MS search. , 2018, Mass spectrometry reviews.

[39]  Emma L. Schymanski,et al.  Exploring the Potential of a Global Emerging Contaminant Early Warning Network through the Use of Retrospective Suspect Screening with High-Resolution Mass Spectrometry. , 2018, Environmental science & technology.

[40]  Reza Aalizadeh,et al.  Development and application of retention time prediction models in the suspect and non-target screening of emerging contaminants. , 2019, Journal of hazardous materials.

[41]  Xin Wang,et al.  Untargeted screening of unknown xenobiotics and potential toxins in plasma of poisoned patients using high-resolution mass spectrometry: Generation of xenobiotic fingerprint using background subtraction. , 2016, Analytica chimica acta.

[42]  Malcolm J. Reid,et al.  Assessing sample extraction efficiencies for the analysis of complex unresolved mixtures of organic pollutants: A comprehensive non-target approach. , 2018, Analytica chimica acta.

[43]  Herbert Oberacher,et al.  Successful adaption of a forensic toxicological screening workflow employing nontargeted liquid chromatography‐tandem mass spectrometry to water analysis , 2016, Electrophoresis.

[44]  Matthias Müller-Hannemann,et al.  In silico fragmentation for computer assisted identification of metabolite mass spectra , 2010, BMC Bioinformatics.

[45]  K. Tollefsen,et al.  Effect-directed identification of naphthenic acids as important in vitro xeno-estrogens and anti-androgens in North sea offshore produced water discharges. , 2009, Environmental science & technology.

[46]  Alexander Makarov,et al.  Petroleomics via Orbitrap mass spectrometry with resolving power above 1 000 000 at m/z 200 , 2018, RSC advances.

[47]  B. W. Wright,et al.  Using Receiver Operating Characteristic Curves To Optimize Discovery-Based Software with Comprehensive Two-Dimensional Gas Chromatography with Time-of-Flight Mass Spectrometry. , 2017, Analytical chemistry.

[48]  Masanori Arita,et al.  MS-DIAL: Data Independent MS/MS Deconvolution for Comprehensive Metabolome Analysis , 2015, Nature Methods.

[49]  Emma L. Schymanski,et al.  Strategies to characterize polar organic contamination in wastewater: exploring the capability of high resolution mass spectrometry. , 2014, Environmental science & technology.

[50]  Richard G. Brereton,et al.  Applied Chemometrics for Scientists , 2007 .

[51]  Syam S Andra,et al.  Trends in the application of high-resolution mass spectrometry for human biomonitoring: An analytical primer to studying the environmental chemical space of the human exposome. , 2017, Environment international.

[52]  Rainer Breitling,et al.  Increasing the mass accuracy of high‐resolution LC‐MS data using background ions – a case study on the LTQ‐Orbitrap , 2008, Proteomics.

[53]  Philip K Hopke,et al.  Comprehensive Emerging Chemical Discovery: Novel Polyfluorinated Compounds in Lake Michigan Trout. , 2016, Environmental science & technology.

[54]  D. Arndt,et al.  A complex matrix characterization approach, applied to cigarette smoke, that integrates multiple analytical methods and compound identification strategies for non‐targeted liquid chromatography with high‐resolution mass spectrometry , 2020, Rapid communications in mass spectrometry : RCM.

[55]  S. Neumann,et al.  CAMERA: an integrated strategy for compound spectra extraction and annotation of liquid chromatography/mass spectrometry data sets. , 2012, Analytical chemistry.

[56]  Emma L. Schymanski,et al.  Mind the Gap: Mapping Mass Spectral Databases in Genome-Scale Metabolic Networks Reveals Poorly Covered Areas , 2018, Metabolites.

[57]  Oliver Fiehn,et al.  Advances in structure elucidation of small molecules using mass spectrometry , 2010, Bioanalytical reviews.

[58]  J. Fenn,et al.  Electrospray interface for liquid chromatographs and mass spectrometers. , 1985, Analytical chemistry.

[59]  Wolfgang Schulz,et al.  Application of Non-Target Analysis with LC-HRMS for the Monitoring of Raw and Potable Water: Strategy and Results: Assessing Transformation Products of Chemicals by Non-Target and Suspect Screening − Strategies and Workflows Volume 2 , 2016 .

[60]  Matthias Hamburger,et al.  Application of liquid chromatography-atmospheric pressure ionization mass spectrometry in natural product analysis evaluation and optimization of electrospray and heated nebulizer interfaces , 1996 .

[61]  Christophe Junot,et al.  Mass spectrometry for the identification of the discriminating signals from metabolomics: current status and future trends. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[62]  Emma L. Schymanski,et al.  Prioritizing Unknown Transformation Products from Biologically-Treated Wastewater Using High-Resolution Mass Spectrometry, Multivariate Statistics, and Metabolic Logic. , 2015, Analytical chemistry.

[63]  Emma L. Schymanski,et al.  Nontarget Screening with High Resolution Mass Spectrometry in the Environment: Ready to Go? , 2017, Environmental science & technology.

[64]  Ronald A Hites,et al.  Is Nontargeted Screening Reproducible? , 2018, Environmental science & technology.

[65]  Bhagwat Prasad,et al.  Critical Issues and Optimized Practices in Quantification of Protein Abundance Level to Determine Interindividual Variability in DMET Proteins by LC‐MS/MS Proteomics , 2018, Clinical pharmacology and therapeutics.

[66]  Torsten C. Schmidt,et al.  Recent trends in water analysis triggering future monitoring of organic micropollutants , 2018, Analytical and Bioanalytical Chemistry.

[67]  D. Zimmer.  Introduction to quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) , 2003 .

[68]  Heinz Singer,et al.  Alleviating the reference standard dilemma using a systematic exact mass suspect screening approach with liquid chromatography-high resolution mass spectrometry. , 2013, Analytical chemistry.

[69]  A. Furey,et al.  Ion suppression; a critical review on causes, evaluation, prevention and applications. , 2013, Talanta.

[70]  Herbert Oberacher,et al.  Annotating Nontargeted LC-HRMS/MS Data with Two Complementary Tandem Mass Spectral Libraries , 2018, Metabolites.

[71]  Ann M. Richard,et al.  Using prepared mixtures of ToxCast chemicals to evaluate non-targeted analysis (NTA) method performance , 2019, Analytical and Bioanalytical Chemistry.

[72]  Johannes P C Vissers,et al.  Scanning Quadrupole Data-Independent Acquisition, Part A: Qualitative and Quantitative Characterization. , 2017, Journal of proteome research.

[73]  Alessandra Gentili,et al.  Analysis of antithyroid drugs in surface water by using liquid chromatography-tandem mass spectrometry. , 2014, Journal of chromatography. A.

[74]  Emma L. Schymanski,et al.  Identifying small molecules via high resolution mass spectrometry: communicating confidence. , 2014, Environmental science & technology.

[75]  W. Niessen,et al.  Liquid chromatography-mass spectrometry in occupational toxicology: a novel approach to the study of biotransformation of industrial chemicals. , 2004, Journal of chromatography. A.

[76]  Mélanie Desrosiers,et al.  A review of what is an emerging contaminant , 2014, Chemistry Central Journal.

[77]  F. Hernández,et al.  Current use of high-resolution mass spectrometry in the environmental sciences , 2012, Analytical and Bioanalytical Chemistry.

[78]  Malcolm J Reid,et al.  Letter to the Editor: Optimism for Nontarget Analysis in Environmental Chemistry. , 2019, Environmental science & technology.

[79]  Steffen Neumann,et al.  IPO: a tool for automated optimization of XCMS parameters , 2015, BMC Bioinformatics.

[80]  Félix Hernández,et al.  Target and non-target screening strategies for organic contaminants, residues and illicit substances in food, environmental and human biological samples by UHPLC-QTOF-MS , 2012 .

[81]  John G. Sled,et al.  Compositional space: A guide for environmental chemists on the identification of persistent and bioaccumulative organics using mass spectrometry. , 2019, Environment international.

[82]  Romà Tauler,et al.  Data analysis strategies for targeted and untargeted LC-MS metabolomic studies: Overview and workflow , 2016 .

[83]  Bertrand Rochat,et al.  Proposed Confidence Scale and ID Score in the Identification of Known-Unknown Compounds Using High Resolution MS Data , 2017, Journal of The American Society for Mass Spectrometry.

[84]  Malcolm J Reid,et al.  Statistical Variable Selection: An Alternative Prioritization Strategy during the Nontarget Analysis of LC-HR-MS Data. , 2017, Analytical chemistry.

[85]  Piero R. Gardinali,et al.  Assessing accuracy, precision and selectivity using quality controls for non-targeted analysis. , 2020, The Science of the total environment.

[86]  Thomas Letzel,et al.  LC-MS screening techniques for wastewater analysis and analytical data handling strategies: Sartans and their transformation products as an example. , 2015, Chemosphere.

[87]  Robert Mistrik,et al.  Applications of Fourier Transform Ion Cyclotron Resonance (FT-ICR) and Orbitrap Based High Resolution Mass Spectrometry in Metabolomics and Lipidomics , 2016, International journal of molecular sciences.

[88]  Emma L. Schymanski,et al.  Metabolite identification: are you sure? And how do your peers gauge your confidence? , 2014, Metabolomics.

[89]  Maarten Honing,et al.  Exploring the boundaries of bioanalytical quantitative LC–MS–MS , 2000 .

[90]  Martin Krauss,et al.  Identification of novel micropollutants in wastewater by a combination of suspect and nontarget screening. , 2014, Environmental pollution.

[91]  Steffen Neumann,et al.  Highly sensitive feature detection for high resolution LC/MS , 2008, BMC Bioinformatics.

[92]  Malcolm J Reid,et al.  Combining a Deconvolution and a Universal Library Search Algorithm for the Nontarget Analysis of Data-Independent Acquisition Mode Liquid Chromatography-High-Resolution Mass Spectrometry Results. , 2018, Environmental science & technology.

[93]  Thomas Letzel,et al.  Non-target screening with high-resolution mass spectrometry: critical review using a collaborative trial on water analysis , 2015, Analytical and Bioanalytical Chemistry.

[94]  Mohammad Talebi,et al.  Benchmarking of Computational Methods for Creation of Retention Models in Quantitative Structure-Retention Relationships Studies , 2017, J. Chem. Inf. Model..

[95]  Pavel Jandera,et al.  Recent advances in stationary phases and understanding of retention in hydrophilic interaction chromatography. A review. , 2017, Analytica chimica acta.

[96]  Emma L. Schymanski,et al.  Suspect and nontarget screening approaches to identify organic contaminant records in lake sediments , 2014, Analytical and Bioanalytical Chemistry.

[97]  Alan G. Marshall,et al.  Truly “exact” mass: Elemental composition can be determined uniquely from molecular mass measurement at ∼0.1 mDa accuracy for molecules up to ∼500 Da , 2006 .

[98]  Bernhard O. Palsson,et al.  Ion Mobility Derived Collision Cross Sections to Support Metabolomics Applications , 2014, Analytical chemistry.

[99]  C. Horváth,et al.  Liquid Chromatography with Hydrocarbonaceous Bonded Phases; Theory and Practice of Reversed Phase Chromatography , 1977 .

[100]  D. McCalley,et al.  Understanding and manipulating the separation in hydrophilic interaction liquid chromatography. , 2017, Journal of chromatography. A.

[101]  Boris L. Milman,et al.  The chemical space for non-target analysis , 2017 .

[102]  Uwe Kunkel,et al.  Development and validation of a generic nontarget method based on liquid chromatography - high resolution mass spectrometry analysis for the evaluation of different wastewater treatment options. , 2015, Journal of chromatography. A.

[103]  Antony J. Williams,et al.  ChemSpider:: An Online Chemical Information Resource , 2010 .

[104]  Kristie Thompson,et al.  Rapid screening and identification of chemical hazards in surface and drinking water using high resolution mass spectrometry and a case-control filter. , 2017, Chemosphere.

[105]  Janusz Pawliszyn,et al.  Sample preparation with solid phase microextraction and exhaustive extraction approaches: Comparison for challenging cases. , 2015, Analytica chimica acta.

[106]  Boyoung Han,et al.  A rapid non-target screening method for determining prohibited substances in human urine using liquid chromatography/high-resolution tandem mass spectrometry. , 2018, Drug testing and analysis.

[107]  P. Urban,et al.  Advances in ultrasensitive mass spectrometry of organic molecules. , 2013, Chemical Society reviews.

[108]  Wolfgang Schulz,et al.  LC-HRMS Data Processing Strategy for Reliable Sample Comparison Exemplified by the Assessment of Water Treatment Processes. , 2017, Analytical chemistry.

[109]  Anne Togola,et al.  Environmental forensics in groundwater coupling passive sampling and high resolution mass spectrometry for screening. , 2016, The Science of the total environment.

[110]  Stacy D. Brown,et al.  Identification of “Known Unknowns” Utilizing Accurate Mass Data and Chemical Abstracts Service Databases , 2011, Journal of the American Society for Mass Spectrometry.

[111]  Susan E Abbatiello,et al.  Effect of collision energy optimization on the measurement of peptides by selected reaction monitoring (SRM) mass spectrometry. , 2010, Analytical chemistry.

[112]  Malcolm J. Reid,et al.  A Self Adjusting Algorithm for the Non-targeted Feature Detection of High Resolution Mass Spectrometry Coupled with Liquid Chromatography Profile Data. , 2019, Analytical chemistry.

[113]  Joerg Hippler,et al.  Contaminant screening of wastewater with HPLC-IM-qTOF-MS and LC+LC-IM-qTOF-MS using a CCS database , 2016, Analytical and Bioanalytical Chemistry.

[114]  Stephen E Stein,et al.  Quality control for building libraries from electrospray ionization tandem mass spectra. , 2014, Analytical chemistry.

[115]  Godfrey Ruth,et al.  Guide to achieving reliable quantitative LC-MS measurements , 2013 .

[116]  Ludovic C. Gillet,et al.  Targeted Data Extraction of the MS/MS Spectra Generated by Data-independent Acquisition: A New Concept for Consistent and Accurate Proteome Analysis* , 2012, Molecular & Cellular Proteomics.

[117]  Michael Neumann,et al.  Mind the Gap: Persistent and Mobile Organic Compounds-Water Contaminants That Slip Through. , 2016, Environmental science & technology.

[118]  Arjen Lommen,et al.  MetAlign: interface-driven, versatile metabolomics tool for hyphenated full-scan mass spectrometry data preprocessing. , 2009, Analytical chemistry.

[119]  Tianwei Yu,et al.  apLCMS - adaptive processing of high-resolution LC/MS data , 2009, Bioinform..

[120]  Xavier Ortiz,et al.  Suspect, non-target and target screening of emerging pollutants using data independent acquisition: Assessment of a Mediterranean River basin. , 2019, The Science of the total environment.

[121]  Malcolm J Reid,et al.  Two stage algorithm vs commonly used approaches for the suspect screening of complex environmental samples analyzed via liquid chromatography high resolution time of flight mass spectroscopy: A test study. , 2017, Journal of chromatography. A.

[122]  E. Champarnaud,et al.  Evaluation of the comparability of spectra generated using a tuning point protocol on twelve electrospray ionisation tandem-in-space mass spectrometers. , 2011, Rapid communications in mass spectrometry : RCM.

[123]  C. Horváth,et al.  Reverse-phase chromatography of polar biological substances: separation of catechol compounds by high-performance liquid chromatography. , 1976, Clinical chemistry.

[124]  Hui Jiang,et al.  Machine learning combined with non-targeted LC-HRMS analysis for a risk warning system of chemical hazards in drinking water: A proof of concept. , 2019, Talanta.

[125]  Edward P. Kolodziej,et al.  Suspect and non-target screening for contaminants of emerging concern in an urban estuary. , 2019, Environmental science & technology.

[126]  Thomas Letzel,et al.  RPLC-HILIC and SFC with Mass Spectrometry: Polarity-Extended Organic Molecule Screening in Environmental (Water) Samples. , 2017, Analytical chemistry.

[127]  Stefan Posch,et al.  Improving MetFrag with statistical learning of fragment annotations , 2019, BMC Bioinformatics.

[128]  Urs Berger,et al.  Occurrence of emerging persistent and mobile organic contaminants in European water samples. , 2019, Water research.

[129]  T. Letzel,et al.  Main interactions and influences of the chromatographic parameters in HILIC separations. , 2013, Journal of chromatographic science.

[130]  Dalibor Štys,et al.  Fundamental definitions and confusions in mass spectrometry about mass assignment, centroiding and resolution , 2014 .

[131]  Oliver Fiehn,et al.  Seven Golden Rules for heuristic filtering of molecular formulas obtained by accurate mass spectrometry , 2007, BMC Bioinformatics.

[132]  John A McLean,et al.  Correlating Resolving Power, Resolution, and Collision Cross Section: Unifying Cross-Platform Assessment of Separation Efficiency in Ion Mobility Spectrometry. , 2017, Analytical chemistry.

[133]  Anna Kärrman,et al.  Novel fluorinated surfactants tentatively identified in firefighters using liquid chromatography quadrupole time-of-flight tandem mass spectrometry and a case-control approach. , 2015, Environmental science & technology.

[134]  Matej Oresic,et al.  MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data , 2010, BMC Bioinformatics.

[135]  Sebastian Böcker,et al.  Fragmentation trees reloaded , 2014, Journal of Cheminformatics.

[136]  Emily Parry,et al.  Comparing targeted and non-targeted high-resolution mass spectrometric approaches for assessing advanced oxidation reactor performance. , 2016, Water research.

[137]  Thomas Ternes,et al.  Utilization of large volume zwitterionic hydrophilic interaction liquid chromatography for the analysis of polar pharmaceuticals in aqueous environmental samples: Benefits and limitations. , 2017, Journal of chromatography. A.

[138]  M. G. Gómez Ramos,et al.  Development of sample extraction and clean-up strategies for target and non-target analysis of environmental contaminants in biological matrices. , 2015, Journal of chromatography. A.

[139]  Malcolm J. Reid,et al.  The effect of extraction methodology on the recovery and distribution of naphthenic acids of oilfield produced water. , 2019, The Science of the total environment.

[140]  Christian Zwiener,et al.  Assessment of N-Oxide Formation during Wastewater Ozonation. , 2017, Environmental science & technology.

[141]  K. Valko,et al.  RP-HPLC Retention Data for Measuring Structural Similarity of Compounds for QSAR Studies , 1987 .

[142]  Emma L. Schymanski,et al.  Statistical approaches for LC-HRMS data to characterize, prioritize, and identify transformation products from water treatment processes , 2016 .

[143]  Emma L. Schymanski,et al.  MetFrag relaunched: incorporating strategies beyond in silico fragmentation , 2016, Journal of Cheminformatics.

[144]  Emma L. Schymanski,et al.  Integrating ion mobility spectrometry into mass spectrometry-based exposome measurements: what can it add and how far can it go? , 2016, Bioanalysis.

[145]  Steffen Neumann,et al.  Metabolome Analysis of Biosynthetic Mutants Reveals a Diversity of Metabolic Changes and Allows Identification of a Large Number of New Compounds in Arabidopsis1[W][OA] , 2008, Plant Physiology.

[146]  Tom Fawcett,et al.  An introduction to ROC analysis , 2006, Pattern Recognit. Lett..

[147]  Susan E. Abbatiello,et al.  Targeted Peptide Measurements in Biology and Medicine: Best Practices for Mass Spectrometry-based Assay Development Using a Fit-for-Purpose Approach* , 2014, Molecular & Cellular Proteomics.

[148]  Gerhard Kattner,et al.  Fundamentals of molecular formula assignment to ultrahigh resolution mass data of natural organic matter. , 2007, Analytical chemistry.

[149]  Ludovic C. Gillet,et al.  Data‐independent acquisition‐based SWATH‐MS for quantitative proteomics: a tutorial , 2018, Molecular systems biology.

[150]  J. Vial,et al.  Reversed-phase liquid chromatography column testing: robustness study of the test. , 2004, Journal of chromatography. A.

[151]  Herbert Oberacher,et al.  A European proposal for quality control and quality assurance of tandem mass spectral libraries , 2020, Environmental Sciences Europe.

[152]  Atefeh Rafiei,et al.  Comparison of peak-picking workflows for untargeted liquid chromatography/high-resolution mass spectrometry metabolomics data analysis. , 2015, Rapid communications in mass spectrometry : RCM.

[153]  Gayatri Mohanty,et al.  Challenges of Proteomic Studies in Human Reproduction , 2016 .