Profiling of Thiol-Containing Compounds by Stable
Isotope Labeling Double Precursor Ion Scan Mass Spectrometry
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Abstract
Here
we developed a novel strategy of isotope labeling in combination
with high-performance liquid chromatography–double precursor
ion scan mass spectrometry (IL–LC–DPIS-MS) analysis
for nontargeted profiling of thiol-containing compounds. In this strategy,
we synthesized a pair of isotope labeling reagents (ω-bromoacetonylquinolinium
bromide, BQB; ω-bromoacetonylquinolinium-<i>d</i><sub>7</sub> bromide, BQB-<i>d</i><sub>7</sub>) that contain
a reactive group, an isotopically labeled moiety, and an ionizable
group to selectively label thiol-containing compounds. The BQB and
BQB-<i>d</i><sub>7</sub> labeled compounds can generate
two characteristic product ions <i>m</i>/<i>z</i> 218 and 225, which contain an isotope tag and therefore were used
for double precursor ion scans in mass spectrometry analysis. The
peak pairs with characteristic mass differences can be readily extracted
from the two precursor ion scan (PIS) spectra and assigned as potential
thiol-containing candidates, which facilitates the identification
of analytes. BQB and BQB-<i>d</i><sub>7</sub> labeled thiol-containing
compounds can be clearly distinguished by generating two individual
ion chromatograms. Thus, thiol-containing compounds from two samples
labeled with different isotope reagents are ionized at the same time
but recorded separately by mass spectrometry, offering good identification
and accurate quantification by eliminating the MS response fluctuation
and mutual interference from the two labeled samples. Using the IL–LC–DPIS-MS
strategy, we profiled the thiol-containing compounds in beer and human
urine, and 21 and 103 thiol candidates were discovered in beer and
human urine, respectively. In addition, 9 and 17 thiol candidates
in beer and human urine were successfully identified by further comparison
with thiol standards or tandem mass spectrometry analysis. Taken together,
the IL–LC–DPIS-MS method is demonstrated to be a promising
strategy in the profiling of compounds with identical groups in metabolomics
study