Analysis of molecular isotopic structures at high precision and accuracy by Orbitrap mass spectrometry

John Eiler, Jaime Cesar, Laura Chimiak, Brooke Dallas, Kliti Grice, Jens Griep-Raming, Dieter Juchelka, Nami Kitchen, Max Lloyd, Alexander Makarov, Richard Robins, Johannes Schwieters

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Several technologies are being developed to examine the intramolecular isotopic structures of molecules (i.e., site-specific and multiple substitution), but limitations in sample size and type or (for mass spectrometry) resolution have so far prevented the creation of a general technique. We have now demonstrated the capacity for precise and accurate study of molecular isotopic contents and structures by Fourier transform mass spectrometry, using instruments containing a Thermo Scientific™ Orbitrap™ mass analyzer, here the Thermo Scientific Q Exactive GC™ and Q Exactive HF™ instruments. Orbitrap mass analyzers achieve mass resolutions in the range ∼250,000–1 M (FWHM) in the mass range of greatest interest to studies of molecular isotopic structure, 50–200 amu. This allows for resolution of many nearly isobaric interferences for compounds containing H, C, N, O and/or S. In this paper we show that internal and external experimental reproducibilities of isotope ratio analyses using the Orbitrap analysis can conform to shot-noise limits down to levels of tenths of per mil (1SE), with similar accuracy when standardized to reference materials. Precision reaches ±0.015‰ for exceptionally long integrations. Such measurements do not call for modifications to the ion optics of the Q Exactive instruments, but do require specially designed sample introduction devices to permit sample/standard comparison and long integration times. The sensitivity of the Q Exactive instruments permit analysis of sub-nanomolar samples and quantification of multiply-substituted species. Site-specific capabilities arise from the fact that mass spectra of molecular analytes commonly contain diverse fragment ion species, each of which samples a specific sub-set of molecular sites.

Original languageEnglish (US)
Pages (from-to)126-142
Number of pages17
JournalInternational Journal of Mass Spectrometry
StatePublished - Nov 2017

All Science Journal Classification (ASJC) codes

  • Instrumentation
  • Condensed Matter Physics
  • Spectroscopy
  • Physical and Theoretical Chemistry


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