High-Resolution Metabolomics Assessment of Military Personnel

Abstract

Objective To maximize detection of serum metabolites with high-resolution metabolomics (HRM). Methods Department of Defense Serum Repository (DoDSR) samples were analyzed using ultra-high resolution mass spectrometry with three complementary chromatographic phases and four ionization modes. Chemical coverage was evaluated by number of ions detected and accurate mass matches to a human metabolomics database. Results Individual HRM platforms provided accurate mass matches for up to 58% of the KEGG metabolite database. Combining two analytical methods increased matches to 72%, and included metabolites in most major human metabolic pathways and chemical classes. Detection and feature quality varied by analytical configuration. Conclusions Dual chromatography HRM with positive and negative electrospray ionization provides an effective generalized method for metabolic assessment of military personnel.

Deployment-Associated Exposure Surveillance With High-Resolution Metabolomics

“…In this analysis, quantified PAH levels of anthracene measured using GC-MS in 30 non-identified serum samples (6, 61) were tested for association with m/z ions detected by HRM matching known adduct masses of PAH metabolites from the KEGG database. Twenty-four metabolites detected using HILIC chromatography with positive electrospray ionization and 18 using reverse-phase chromatography with positive atmospheric chemical ionization (46) were found to be significantly associated with serum PAH levels, supporting the use of HRM for a more comprehensive measure of exposure biomarkers than available from targeted biomonitoring alone. Interestingly, anthracene levels were found to be predominantly associated with naphthalene metabolites (Figure 4B), suggesting possible co-exposures or synergistic metabolism.…”

“…A chemical present in only one sample out of 100 can be reliably measured if it is present in three replicate analyses of a sample (15, 43, 45), even though it is absent from the preceding 99 samples. With further relaxation of precision requirements, such as increasing CV thresholds from 50% to 100% and allowable number of samples with non-detected intensity values (which is justified by the usefulness of information on low abundance and low frequency exposures), >20,000 ions can be measured routinely on a single column; use of dual chromatography increases this to >30,000 ions (46). For high-abundance species, multiple adducts and isotopic forms will be detected based upon the ionization scheme used and molecule functional groups.…”

Putrescine as indicator of manganese neurotoxicity: Dose-response study in human SH-SY5Y cells

“…Electrospray ionization was used in the positive ion mode on the Q-Exactive HF mass spectrometer operating with resolution set to 120,000 and scan range set to 85–1275 m/z (mass to charge) (Liu et al, 2016; Soltow et al, 2013). Ultra-high resolution mass spectrometry operating at 60,000 and 120,000 resolution have previously been shown to provide effective quantification of metabolites in biologic extracts (Accardi et al, 2016; Go et al, 2015b, 2015c, 2015d; Johnson et al, 2008).…”

“…Ultra-high resolution mass spectrometry operating at 60,000 and 120,000 resolution have previously been shown to provide effective quantification of metabolites in biologic extracts (Accardi et al, 2016; Go et al, 2015b, 2015c, 2015d; Johnson et al, 2008). A 2% formic acid/acetonitrile gradient was used as described (Liu et al, 2016). Injection volume was 10 μl and run time was 10 min.…”

Computational Metabolomics: A Framework for the Million Metabolome

“…The rapid advance in instrument quality is illustrated by a recent HRM study showing that chemicals could be quantified that differed by approximately 8 orders of magnitude in absolute abundance. 15 Thus, even though the best platforms for cost, coverage, and quantitative reproducibility are not well established, use of mass spectrometry protocols with simple protein removal, dual chromatography, dual electrospray ionization, and triplicate analyses 3,22 provides far more healthrelated chemical information than contemporary blood chemistry, NMR methods, or other analytical procedures. This is not to imply that NMR spectroscopy and other methods have no place in health analyses, only that based on cost and extent of information provided, HRM offers advantages (discussed in Jones et al).…”