Quantification Approaches in Non-Target LC/ESI/HRMS Analysis: An Interlaboratory Comparison

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.