High-Performance Data Processing Workflow Incorporating Effect-Directed Analysis for Feature Prioritization in Suspect and Nontarget Screening

Tim J H Jonkers, Jeroen Meijer, Jelle J Vlaanderen, Roel C H Vermeulen, Corine J Houtman, Timo Hamers, Marja H Lamoree

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Effect-directed analysis (EDA) aims at the detection of bioactive chemicals of emerging concern (CECs) by combining toxicity testing and high-resolution mass spectrometry (HRMS). However, consolidation of toxicological and chemical analysis techniques to identify bioactive CECs remains challenging and laborious. In this study, we incorporate state-of-the-art identification approaches in EDA and propose a robust workflow for the high-throughput screening of CECs in environmental and human samples. Three different sample types were extracted and chemically analyzed using a single high-performance liquid chromatography HRMS method. Chemical features were annotated by suspect screening with several reference databases. Annotation quality was assessed using an automated scoring system. In parallel, the extracts were fractionated into 80 micro-fractions each covering a couple of seconds from the chromatogram run and tested for bioactivity in two bioassays. The EDA workflow prioritized and identified chemical features related to bioactive fractions with varying levels of confidence. Confidence levels were improved with the in silico software tools MetFrag and the retention time indices platform. The toxicological and chemical data quality was comparable between the use of single and multiple technical replicates. The proposed workflow incorporating EDA for feature prioritization in suspect and nontarget screening paves the way for the routine identification of CECs in a high-throughput manner.

Original languageEnglish
Pages (from-to)1639-1651
Number of pages13
JournalEnvironmental Science & Technology
Volume56
Issue number3
Early online date20 Jan 2022
DOIs
Publication statusPublished - 1 Feb 2022

Keywords

  • TTR-binding
  • antibiotic
  • bioassay
  • effect-directed analysis
  • environment
  • suspect and nontarget screening

Fingerprint

Dive into the research topics of 'High-Performance Data Processing Workflow Incorporating Effect-Directed Analysis for Feature Prioritization in Suspect and Nontarget Screening'. Together they form a unique fingerprint.

Cite this