Nontargeted screening (NTS) utilizing liquid chromatography electrospray ionization high-resolution mass spectrometry (LC/ESI/HRMS) is increasingly used to identify environmental contaminants. Major differences in the ionization efficiency of compounds in ESI/HRMS result in widely varying responses and complicate quantitative analysis. Despite an increasing number of methods for quantification without authentic standards in NTS, the approaches are evaluated on limited and diverse data sets with varying chemical coverage collected on different instruments, complicating an unbiased comparison. In this interlaboratory comparison, organized by the NORMAN Network, we evaluated the accuracy and performance variability of five quantification approaches across 41 NTS methods from 37 laboratories. Three approaches are based on surrogate standard quantification (parent-transformation product, structurally similar or close eluting) and two on predicted ionization efficiencies (RandFor-IE and MLR-IE). Shortly, HPLC grade water, tap water, and surface water spiked with 45 compounds at 2 concentration levels were analyzed together with 41 calibrants at 6 known concentrations by the laboratories using in-house NTS workflows. The accuracy of the approaches was evaluated by comparing the estimated and spiked concentrations across quantification approaches, instrumentation, and laboratories. The RandFor-IE approach performed best with a reported mean prediction error of 15× and over 83% of compounds quantified within 10× error. Despite different instrumentation and workflows, the performance was stable across laboratories and did not depend on the complexity of water matrices.

Acquedotto Pugliese SpA Direzione Laboratori e Controllo Igienico Sanitario 70123 Bari Italy

Agenzia Regionale per l'Ambiente Toscana Via G Marradi 114 57126 Livorno Italy

Analytical Chemistry Group Department of Plant and Environmental Sciences University of Copenhagen Thorvaldsenvej 40 1871 Frederiksberg Denmark

Analytisches Forschungsinstitut für Non Target Screening GmbH Am Mittleren Moos 48 86167 Augsburg Germany

Bavarian Environment Agency Bürgermeister Ulrich Str 160 86179 Augsburg Germany

BRGM 3 avenue Claude Guillemin BP36009 45060 Orléans Cedex 2 France

Center for Omics Sciences IRCCS San Raffaele Scientific Institute 20132 Milan Italy

Department for Organic Environmental Chemistry Helmholtz Centre Hereon Max Planck Str 1 21502 Geesthacht Germany

Department of Aquatic Sciences and Assessment Swedish University of Agricultural Sciences 75007 Uppsala Sweden

Department of Chemistry University of Bath Bath BA2 7AY U K

Department of Chemistry Vienna BOKU University Muthgasse 18 1190 Vienna Austria

Department of Environmental Health Sciences Yale School of Public Health Yale University New Haven Connecticut 06510 United States

Department of Environmental Science Stockholm University Svante Arrhenius väg 8 11418 Stockholm Sweden

Department of Materials and Environmental Chemistry Stockholm University Svante Arrhenius väg 16 11418 Stockholm Sweden

Eawag Swiss Federal Institute of Aquatic Science and Technology Überlandstrasse 133 8600 Dübendorf Switzerland

Environmental and Public Health Analytical Chemistry Research Institute for Pesticides and Water University Jaume 1 12006 Castelló Spain

Environmental Institute Okružná 784 42 97241 Koš Slovak Republic

Environmental Metabolomics Lab Aarhus University Frederiksborgsvej 399 4000 Roskilde Denmark

Het Waterlaboratorium J W Lucasweg 2 2031 BE Haarlem The Netherlands

Human Exposure to Organic Pollutants Unit Institute of Environmental Assessment and Water Research C Jordi Girona 18 26 ES 08034 Barcelona Spain

IBED Environmental Chemistry and Mass Spectrometry Laboratories University of Amsterdam Science Park 904 1098 XH Amsterdam The Netherlands

Institute for Analytical Research Hochschulen Fresenius gem Trägergesellschaft mbH 65510 Idstein Germany

Institute for Biodiversity and Ecosystem Dynamics University of Amsterdam 1012 WP Amsterdam Netherlands

Institute for Sustainability Bath BA2 7AY U K

KWR Water Research Institute Groningenhaven 7 3433 PE Nieuwegein The Netherlands

Laboratory for Operation Control and Research Zweckverband Landeswasserversorgung Am Spitzigen Berg 1 89129 Langenau Germany

Laboratory of Analytical Chemistry Department of Chemistry National and Kapodistrian University of Athens Panepistimiopolis Zografou 15771 Athens Greece

LEESU Univ Paris Est Creteil Ecole des Ponts F 94010 Creteil France

Luxembourg Centre for Systems Biomedicine University of Luxembourg 6 Avenue du Swing L 4367 Belvaux Luxembourg

Ministry of Infrastructure and Water Management Rijkswaterstaat Laboratory Zuiderwagenplein 2 8224 AD Lelystad The Netherlands

NILU Instituttveien 18 2007 Kjeller Norway

Quantem Analytics 51008 Tartu Estonia

Queensland Alliance for Environmental Health Sciences The University of Queensland Woolloongabba Queensland 4102 Australia

RECETOX Faculty of Science Masaryk University Kamenice 753 5 Building D29 62500 Brno Czech Republic

Research Institute for Geo Hydrological Protection Via Amendola 122 1 70126 Bari Italy

SUEZ CIRSEE 38 rue du president Wilson 78230 Le Pecq France

T G Masaryk Water Research Institute p r i Macharova 5 70200 Ostrava Czech Republic

Toxicological Centre University of Antwerp Universiteitsplein 1 2610 Antwerp Belgium

Univ Paris Est Creteil CNRS OSU EFLUVE F 94010 Creteil France

Universite Claude Bernard Lyon 1 CNRS ISA UMR5280 5 rue de la Doua F 69100 Villeurbanne France

US National Institute of Standards and Technology 331 Fort Johnson Rd 29412 Charleston South Carolina United States

VEOLIA Recherche et Innovation Chemin de la Digue 78600 Maisons Laffitte France

Vlaamse Milieumaatschappij Raymonde de Larochelaan 1 9051 Gent Sint Denijs Westerem Belgium

Water Environmental and Food Chemistry Unit Institute of Environmental Assessment and Water Research C Jordi Girona 18 26 ES 08034 Barcelona Spain

Water Research Institute via del Mulino 19 20861 Brugherio MB Italy

Water Research Institute Via F De Blasio 5 70132 Bari Italy

White Lab Srl Via Mons Rodolfi 22 36022 San Giuseppe de Cassola Italy

WLN Rijksstraatweg 85 9756 AD Glimmen Groningen The Netherlands

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