Quantification\nApproaches in Non-Target LC/ESI/HRMS\nAnalysis: An Interlaboratory Comparison

Nontargeted screening (NTS) utilizing liquid chromatography\nelectrospray\nionization high-resolution mass spectrometry (LC/ESI/HRMS) is increasingly\nused to identify environmental contaminants. Major differences in\nthe ionization efficiency of compounds in ESI/HRMS result in widely\nvarying responses and complicate quantitative analysis. Despite an\nincreasing number of methods for quantification without authentic\nstandards in NTS, the approaches are evaluated on limited and diverse\ndata sets with varying chemical coverage collected on different instruments,\ncomplicating an unbiased comparison. In this interlaboratory comparison,\norganized by the NORMAN Network, we evaluated the accuracy and performance\nvariability of five quantification approaches across 41 NTS methods\nfrom 37 laboratories. Three approaches are based on surrogate standard\nquantification (parent-transformation product, structurally similar\nor close eluting) and two on predicted ionization efficiencies (RandFor-<i>IE</i> and MLR-<i>IE</i>). Shortly, HPLC grade water,\ntap water, and surface water spiked with 45 compounds at 2 concentration\nlevels were analyzed together with 41 calibrants at 6 known concentrations\nby the laboratories using in-house NTS workflows. The accuracy of\nthe approaches was evaluated by comparing the estimated and spiked\nconcentrations across quantification approaches, instrumentation,\nand laboratories. The RandFor-<i>IE</i> approach performed\nbest with a reported mean prediction error of 15× and over 83%\nof compounds quantified within 10× error. Despite different instrumentation\nand workflows, the performance was stable across laboratories and\ndid not depend on the complexity of water matrices.