TY - JOUR
T1 - Analysis of molecular isotopic structures at high precision and accuracy by Orbitrap mass spectrometry
AU - Eiler, John
AU - Cesar, Jaime
AU - Chimiak, Laura
AU - Dallas, Brooke
AU - Grice, Kliti
AU - Griep-Raming, Jens
AU - Juchelka, Dieter
AU - Kitchen, Nami
AU - Lloyd, Max
AU - Makarov, Alexander
AU - Robins, Richard
AU - Schwieters, Johannes
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/11
Y1 - 2017/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ijms.2017.10.002
DO - 10.1016/j.ijms.2017.10.002
M3 - Article
AN - SCOPUS:85031745195
SN - 1387-3806
VL - 422
SP - 126
EP - 142
JO - International Journal of Mass Spectrometry
JF - International Journal of Mass Spectrometry
ER -