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

Abstract

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.

Quaternary Ammonium Compounds in Paired Human Urine and Feces: Relative Significance of Biliary Elimination

“…This distribution profile is similar to those reported for dog feces (64%, 33%, 0.2%, and 3.5% for BACs, DDACs, BACm, and ATMACs, respectively), cat feces (57%, 34%, 0.3%, and 9.1%, respectively), and indoor dust (56%, 26%, and 18% for BACs, DDACs, ATMACs, respectively). , The composition of BACs was 64% of ∑All in disinfecting products . Nevertheless, a different composition of QACs was found in human serum and breast milk, in which DDACs were minor components, accounting for <2% of ∑All, , suggesting that DDACs may be metabolized . Furthermore, DDACs may be preferentially sequestered in body tissues.…”

“…C12- and C14-BACs are high-production-volume chemicals in the United States, with annual production volumes exceeding 0.45 million kilograms . The fecal concentrations of C12–C16 BACs (median: 0.03–30.6 ng/g ww) measured in this study were 2- to 35-fold lower than those measured in an earlier study (1.06–106 ng/g ww) . Among BACm, C8–C12 COOH-BACs and OH-C12-BAC were frequently detected in human feces.…”

“…Further toxicological and epidemiological studies are warranted to investigate the toxicities of QACs and their metabolites following chronic exposure. Given the presence of other metabolites of QACs in human urine and feces, our calculation is an underestimate of the actual exposure doses.…”

“…In contrast, ATMACs accounted for 50% and 27% of ∑All in human serum and breast milk, respectively. , The differences in the composition of ATMACs between feces/urine and serum/breast milk suggest the existence of metabolites of these chemicals in urine/feces. A recent study identified four metabolites of ATMACs in human feces . Nevertheless, analytical standards to quantify ATMAC metabolites are not commercially available.…”

“…In contrast, only COOH-BACs were found, at median concentrations of 0.28 and 2.08 ng/mL in cat and dog urine, respectively . Besides, a recent study identified 13 parent QACs and 35 metabolites in five human feces samples, with median concentrations of C12–C16 BACs at 1.06–106 ng/g wet weight (ww) . Nevertheless, DDACs, ATMACs, and the metabolites of QACs have never been quantified in human feces.…”