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.

Non-targeted and suspect analyses with liquid chromatography/electrospray/high-resolution mass spectrometry (LC/ESI/HRMS) are gaining importance as they enable identification of hundreds or even thousands of compounds in a single sample. Here, we present an approach to address the challenge to quantify compounds identified from LC/HRMS data without authentic standards. The approach uses random forest regression to predict the response of the compounds in ESI/HRMS with a mean error of 2.2 and 2.0 times for ESI positive and negative mode, respectively. We observe that the predicted responses can be transferred between different instruments via a regression approach. Furthermore, we applied the predicted responses to estimate the concentration of the compounds without the standard substances. The approach was validated by quantifying pesticides and mycotoxins in six different cereal samples. For applicability, the accuracy of the concentration prediction needs to be compatible with the effect (e.g. toxicology) predictions. We achieved the average quantification error of 5.4 times, which is well compatible with the accuracy of the toxicology predictions.