Citation:

Aalizadeh, R., N. Alygizakis, E. Schymanski, M. Krauss, T. Schulze, M. Ibanez, A. McEachran, A. Chao, A. Williams, P. Gago-Ferrero, A. Covaci, C. Moschet, T. Young, J. Hollender, J. Slobodnik, AND N. Thomaidis. Development and Application of Liquid Chromatographic Retention Time Indices in HRMS-Based Suspect and Nontarget Screening. Analytical Chemistry. American Chemical Society, Washington, DC, 93(33):11601-11611, (2021). https://doi.org/10.1021/acs.analchem.1c02348

Impact/Purpose:

Suspect, Targeted and Non-targeted Analysis mass spectrometry approaches all utilize the CompTox Chemicals Dashboard and associated meta-data streams. Advanced search capabilities supporting mass spectrometry based data analysis (all forms of targeted and non-targeted analysis) to support data required for more quantitative exposure modeling can be utilized for rapid screening of chemical risk. This includes mass spectral data searching of experimental versus predicted data and other advanced candidate ranking approaches. This product provides regulatory scientists, students and researchers with the ability to effectively access and exploit the many different data streams available in the EPA's CompTox Chemicals Dashboard to support different regulatory purposes and supports current Agency efforts to reduce mammal study requests by 30% by 2025, and completely eliminate all mammal study requests and funding by 2035.

Description:

There is an increasing need for comparable and harmonized retention times (tR) in liquid chromatography (LC) among different laboratories, to provide supplementary evidence for the identity of compounds in high-resolution mass spectrometry (HRMS)-based suspect and nontarget screening investigations. In this study, a rigorously tested, flexible, and less system-dependent unified retention time index (RTI) approach for LC is presented, based on the calibration of the elution pattern. Two sets of 18 calibrants were selected for each of ESI+ and ESI-based on the maximum overlap with the retention times and chemical similarity indices from a total set of 2123 compounds. The resulting calibration set, with RTI set to range between 1 and 1000, was proposed as the most appropriate RTI system after rigorous evaluation, coordinated by the NORMAN network. The validation of the proposed RTI system was done externally on different instrumentation and LC conditions. The RTI can also be used to check the reproducibility and quality of LC conditions. Two quantitative structure–retention relationship (QSRR)-based models were built based on the developed RTI systems, which assist in the removal of false-positive annotations. The applicability domains of the QSRR models allowed completing the identification process with higher confidence for substances within the domain, while indicating those substances for which results should be treated with caution. The proposed RTI system was used to improve confidence in suspect and nontarget screening and increase the comparability between laboratories as demonstrated for two examples. All RTI-related calculations can be performed online at http://rti.chem.uoa.gr/.

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