LC-Mass Spectrometer for Intramolecular Isotope Ratios at Natural Isotopic Abundance

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Compound-specific isotope analysis (CSIA) has revolutionized the detection and characterization of organic contaminant degradation in the environment. Gas- or liquid-chromatography (GC, LC) in sequence with online conversion and subsequent isotope ratio mass spectrometry (IRMS) has allowed accessing a previously untapped source of information: the ratio of naturally occurring stable isotopes (13C/12C, 15N/14N, etc.) within molecules. Isotopic fingerprinting can elucidate the different origins of organic chemicals in cases of groundwater contamination. Gradual changes in contaminant isotope ratios over time and space can detect natural contaminant degradation, and even underlying transformation mechanisms. However, research in Environmental Chemistry has moved on from the foundation of CSIA’s success story (i.e., non-polar highly concentrated legacy contaminants of low molecular weight) to explore the behavior of more polar chemicals of high molecular weight and at low concentrations (e.g. pesticides or pharmaceuticals). This narrows the window of opportunity for CSIA. First, polar compounds of high molecular weight are often not compatible with GC and require liquid-chromatography involving organic eluents. This presently precludes CSIA of these target compounds. Second, isotope effects of degradation typically occur in only one molecular position and are “diluted out” when molecular size increases. This puts an intrinsic limit to assessing larger compounds based on compound-average isotope fractionation. Third, molecules of higher molecular weight offer more distinguishable molecular positions for isotopic fingerprinting. This powerful source of information remains untapped when only the compound average is analyzed. We, therefore, apply for instrument funding to explore fragment- or even position-specific isotope analysis in polar organic molecules by liquid injection MS. This will allow us to tap the potential that (i) fragmentation and high mass resolution can access element-specific isotopic information in defined molecular fragments or positions and (ii) that the approach is compatible with polar compounds of higher molecular weight. In recent work, the approach has been demonstrated for comparatively simple compounds such as oxyanions (e.g., nitrate), or taking advantage of the fortuitous existence of standards of known intramolecular isotope distribution (e.g., methionine). With the requested instrument we want to spearhead the approach for important environmental pollutants and biomolecules: (i) synthesize standards with known intramolecular isotopic composition for calibration; (ii) explore isotopic fingerprinting to distinguish sources and biosynthetic fluxes; (iii) access position-specific isotope effects to study transformation reactions; (iv) explore lower limits of precise isotope analysis in environmental samples and (v) spearhead applications to characterize metabolism in biology and medicine.