A Proposed Quality Control Standard Mixture and Its Uses for Evaluating Nontargeted and Suspect Screening LC/HR-MS Method Performance

Nontargeted (NTA) and suspect screening
analyses (SSA) aim to detect
and identify unknown compounds of interest from a given sample. The
complexity and diversity of NTA and SSA methodologies necessitate
the use of a comprehensive quality control standard mixture to determine
if methods are fit for purpose, but to our knowledge, such a standard
has not been developed that can be used by multiple disciplines, nor
is one readily available. This work describes the development and
analysis of a proposed nontargeted standard/quality control mixture
for NTA and SSA applications using liquid chromatography/electrospray
ionization-high resolution-mass spectrometry. Considerations in its
development included achieving diversity of compounds with respect
to elemental composition, molecular weight, retention time, and ionization
in positive and/or negative ion modes, which resulted in the inclusion
of 89 compounds. The utility of the standard mixture was applied on
our own NTA and SSA workflows where sample preparation efficiency
and potential sources of error due to instrumental and data processing
methods were evaluated. Some areas in need of improvement were identified,
such as hydrophilic compound detection and molecular formula generation
for compounds containing fluorine. However, our overall methodology
was found to be fit for purpose and we were able to establish thresholds
to increase reliability and throughput of reported results.