ac1c02673_si_001.pdf (11.48 MB)
Download fileIntegration of Chemical Derivatization and in-Source Fragmentation Mass Spectrometry for High-Coverage Profiling of Submetabolomes
journal contribution
posted on 2021-08-09, 11:33 authored by Na An, Quan-Fei Zhu, Yan-Zhen Wang, Cai-Feng Xiong, Yu-Ning Hu, Yu-Qi FengIn-source fragmentation-based high-resolution
mass spectrometry
(ISF-HRMS) is a potential analytical technique, which is usually used
to profile some specific compounds that can generate diagnostic neutral
loss (NL) or fragment ion (FI) in ion source inherently. However,
the ISF-HRMS method does not work for those compounds that cannot
inherently produce diagnostic NL or FI in ion source. In this study,
a derivatization-based in-source fragmentation-information-dependent
acquisition (DISF-IDA) strategy was proposed for profiling the metabolites
with easily labeled functional groups (submetabolomes) by liquid chromatography-electrospray
ionization-quadrupole time-of-flight mass spectrometry (LC-ESI-Q-TOF
MS). As a proof-of-concept study, 36 carboxylated compounds labeled
with N,N-dimethylethylenediamine
(DMED) were selected as model compounds to examine performance of
DISF-IDA strategy in screening the carboxylated metabolites and acquiring
their MSn spectra. In ESI source, the DEMD-derived carboxylated
compounds were fragmented to produce characteristic neutral losses
of 45.0578, 63.0684, and/or 88.1000 Da that were further used as diagnostic
features for screening the carboxylated metabolites by DISF-IDA-based
LC-Q-TOF MS. Furthermore, high-resolution MSn spectra of
the model compounds were also obtained within a single run of DISF-IDA-based
LC-Q-TOF MS analysis, which contributed to the improvement of the
annotation confidence. To further verify its applicability, DISF-IDA
strategy was used for profiling carboxylated submetabolome in mice
feces. Using this strategy, a total of 351 carboxylated metabolites
were detected from mice feces, of which 178 metabolites (51% of the
total) were positively or putatively identified. Moreover, DISF-IDA
strategy was also demonstrated to be applicable for profiling other
submetabolomes with easily labeled functional groups such as amino,
carbonyl, and cis-diol groups. Overall, our proposed
DISF-IDA strategy is a promising technique for high-coverage profiling
of submetabolomes with easily labeled functional groups in biological
samples.
History
Usage metrics
Read the peer-reviewed publication
Categories
Keywords
DISF-IDA strategysubmetabolomecarboxylated metabolitesLC-ESI-Q-TOFin-Source Fragmentation Mass Spectr...mice fecesDISF-IDA-based LC-Q-TOF MS analysision sourcechromatography-electrospray ionizat...FINLSubmetabolomes In-source fragmentat...DMEDDEMD-derived carboxylated compoundsISF-HRMSderivatization-based in-source frag...36 carboxylated compoundsMS n spectraESIDISF-IDA-based LC-Q-TOF MS351 carboxylated metabolitesmodel compounds