Electrospray-Orbitrap Analysis of Nitrate and Sulfate Isotopologues in Natural Samples: Performance and Constraints
7 affiliations
- 1Univ. Grenoble Alpes, CNRS, IRD, Grenoble-INP, INRAE, IGE, Grenoble38000, France.
- 2International Center for Isotope Effects Research, Nanjing University, Nanjing210023, China.
- 3University of Münster, Münster48149, Germany.
- 4Thermo Fisher Scientific GmbH, Bremen28199, Germany.
- 5Department of Atmospheric and Climate Sciences, University of Washington, Seattle, Washington351640, United States.
- 6Department of Earth and Space Sciences, University of Washington, Seattle, Washington351310, United States.
- 7School of Earth & Environmental Sciences, University of St Andrews, St AndrewsKY16 9TS, United Kingdom.
Abstract
Traditional isotope ratio mass spectrometers are not optimally designed to analyze nonvolatile molecular solutes such as oxyanions or organics. Necessary sample conversion steps, often demanding micromole-scale samples, break chemical bonds and limit oxyanion analyses to elemental isotope ratios. Recent studies enthusiastically promote soft electrospray ionization coupled to high-resolution Orbitrap mass spectrometry (ESI-Orbitrap-MS) for intact-molecule isotopologue analysis. This combination uses widely accessible instrumentation to provide simultaneous multi-isotopologue and clumped isotope analyses using tens of nanomoles of dissolved sample. However, its isotopic capabilities have been evaluated primarily through technical assessments rather than on natural samples, despite the need for matrix sensitivity assessments and robust isotopic calibrations. Here, we establish a framework for natural-sample ESI-Orbitrap-MS isotopologue analysis of nitrate and sulfate, addressing matrix effects, isotopologue calibration, and instrumental stability. We demonstrate strong sensitivity to contaminants at concentrations 1000 times below target analytes and strong temperature-correlated drift over >30 min, highlighting the enhanced need for rigorous sample purification to suppress matrix effects, sample-reference bracketing to overcome drift, and isotopologue calibration to reduce biases and robustly quantify uncertainties. We achieve 0.4–1.3‰ precision and accurate measurements of δ15N-NO3–, δ18O-NO3–, Δ17O-NO3–, δ34S-SO42–, and Δ17O–SO42– relative to traditional techniques, consuming only 20 nmol nitrate or 10 nmol sulfate. We resolve relative nitrate clumped isotope values in ice core samples (Δ15N18O-NO3–: ±2.3‰; Δ18O18O-NO3–: ±3.3‰) yet observe no correlations with bulk nitrate isotopes. These results establish practical guidelines for applying ESI-Orbitrap-MS to isotopologue and clumped isotope analysis of trace analytes in challenging sample matrices under real-world conditions.
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BibTeX
@article{saville2026electrosprayorbitrap,
title = {{Electrospray-Orbitrap Analysis of Nitrate and Sulfate Isotopologues in Natural Samples: Performance and Constraints}},
author = {Jack Saville and Julien Witwicky and Elsa Gautier and Alexis Lamothe and Nils Johannes Kuhlbusch and Becky Alexander and Andrew Schauer and Andrea Burke and Priyesh Prabhat and Eva Stüeken and Joshua Garber and Nicolas Caillon and Joël Savarino},
journal = {Analytical Chemistry},
year = {2026},
month = aug,
doi = {10.1021/acs.analchem.6c00183},
url = {https://hal.science/hal-05752345v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Electrospray-Orbitrap Analysis of Nitrate and Sulfate Isotopologues in Natural Samples: Performance and Constraints
AU - Jack Saville
AU - Julien Witwicky
AU - Elsa Gautier
AU - Alexis Lamothe
AU - Nils Johannes Kuhlbusch
AU - Becky Alexander
AU - Andrew Schauer
AU - Andrea Burke
AU - Priyesh Prabhat
AU - Eva Stüeken
AU - Joshua Garber
AU - Nicolas Caillon
AU - Joël Savarino
PY - 2026
DA - 2026/08/31
JO - Analytical Chemistry
DO - 10.1021/acs.analchem.6c00183
UR - https://hal.science/hal-05752345v1
AB - Traditional isotope ratio mass spectrometers are not optimally designed to analyze nonvolatile molecular solutes such as oxyanions or organics. Necessary sample conversion steps, often demanding micromole-scale samples, break chemical bonds and limit oxyanion analyses to elemental isotope ratios. Recent studies enthusiastically promote soft electrospray ionization coupled to high-resolution Orbitrap mass spectrometry (ESI-Orbitrap-MS) for intact-molecule isotopologue analysis. This combination uses widely accessible instrumentation to provide simultaneous multi-isotopologue and clumped isotope analyses using tens of nanomoles of dissolved sample. However, its isotopic capabilities have been evaluated primarily through technical assessments rather than on natural samples, despite the need for matrix sensitivity assessments and robust isotopic calibrations. Here, we establish a framework for natural-sample ESI-Orbitrap-MS isotopologue analysis of nitrate and sulfate, addressing matrix effects, isotopologue calibration, and instrumental stability. We demonstrate strong sensitivity to contaminants at concentrations 1000 times below target analytes and strong temperature-correlated drift over >30 min, highlighting the enhanced need for rigorous sample purification to suppress matrix effects, sample-reference bracketing to overcome drift, and isotopologue calibration to reduce biases and robustly quantify uncertainties. We achieve 0.4–1.3‰ precision and accurate measurements of δ15N-NO3–, δ18O-NO3–, Δ17O-NO3–, δ34S-SO42–, and Δ17O–SO42– relative to traditional techniques, consuming only 20 nmol nitrate or 10 nmol sulfate. We resolve relative nitrate clumped isotope values in ice core samples (Δ15N18O-NO3–: ±2.3‰; Δ18O18O-NO3–: ±3.3‰) yet observe no correlations with bulk nitrate isotopes. These results establish practical guidelines for applying ESI-Orbitrap-MS to isotopologue and clumped isotope analysis of trace analytes in challenging sample matrices under real-world conditions.
SN - 0003-2700
SN - 1520-6882
ER -