Development and Application of a Multidimensional Database for the Detection of Quaternary Ammonium Compounds and Their Phase I Hepatic Metabolites in Humans

The COVID-19 pandemic
has led to significantly increased
human
exposure to the widely used disinfectants quaternary ammonium compounds
(QACs). Xenobiotic metabolism serves a critical role in the clearance
of environmental molecules, yet limited data are available on the
routes of QAC metabolism or metabolite levels in humans. To address
this gap and to advance QAC biomonitoring capabilities, we analyzed
19 commonly used QACs and their phase I metabolites by liquid chromatography–ion
mobility–tandem mass spectrometry (LC–IM–MS/MS).
In vitro generation of QAC metabolites by human liver microsomes produced
a series of oxidized metabolites, with metabolism generally occurring
on the alkyl chain group, as supported by MS/MS fragmentation. Discernible
trends were observed in the gas-phase IM behavior of QAC metabolites,
which, despite their increased mass, displayed smaller collision cross-section
(CCS) values than those of their respective parent compounds. We then
constructed a multidimensional reference SQLite database consisting
of m/z, CCS, retention time (rt), and MS/MS spectra for 19 parent QACs and 81 QAC metabolites.
Using this database, we confidently identified 13 parent QACs and
35 metabolites in de-identified human fecal samples. This is the first
study to integrate in vitro metabolite biosynthesis with LC–IM–MS/MS
for the simultaneous monitoring of parent QACs and their metabolites
in humans.