Large-Scale Implementation and Flaw Investigation of Human Serum Suspect Screening Analysis for Industrial Chemicals

Non-targeted analysis
(NTA), including both suspect screening analysis
(SSA) and unknown compound analysis, has gained increasing popularity
in various fields for its capability in identifying new compounds
of interests. Current major challenges for NTA SSA are that (1) tremendous
effort and resources are needed for large-scale identification and
confirmation of suspect chemicals and (2) suspect chemicals generally
show low matching rates during identification and confirmation processes.
To narrow the gap between these challenges and smooth implementation
of NTA SSA methodology in the biomonitoring field, we present a thorough
SSA workflow for the large-scale screen, identification, and confirmation
of industrial chemicals that may pose adverse health effects in pregnant
women and newborns. The workflow was established in a study of 30
paired maternal and umbilical cord serum samples collected at delivery
in the San Francisco Bay area. By analyzing LC-HRMS and MS/MS data,
together with the assistance of a combination of resources including
online MS/MS spectra libraries, online in silico fragmentation tools,
and the EPA CompTox Chemicals Dashboard, we confirmed the identities
of 17 chemicals, among which monoethylhexyl phthalate, 4-nitrophenol,
tridecanedioic acid, and octadecanedioic acid are especially interesting
due to possible toxicities and their high-volume use in industrial
manufacturing. Similar to other previous studies in the SSA field,
the suspect compounds show relatively low MS/MS identification (16%)
and standard confirmation (8%) rates. Therefore, we also investigated
origins of false positive features and unidentifiable suspected features,
as well as technical obstacles encountered during the confirmation
process, which would promote a better understanding of the flaw of
low confirmation rate and encourage gaining more effective tools for
tackling this issue in NTA SSA.