Identification and Partial Structural Characterization of Mass Isolated Valsartan and Its Metabolite with Messenger Tagging Vibrational Spectroscopy

  • Olga Gorlova
  • Sean M. Colvin
  • Antonio Brathwaite
  • Fabian S. Menges
  • Stephanie M. Craig
  • Scott J. Miller
  • Mark A. Johnson
Research Article


Recent advances in the coupling of vibrational spectroscopy with mass spectrometry create new opportunities for the structural characterization of metabolites with great sensitivity. Previous studies have demonstrated this scheme on 300 K ions using very high power free electron lasers in the fingerprint region of the infrared. Here we extend the scope of this approach to a single investigator scale as well as extend the spectral range to include the OH stretching fundamentals. This is accomplished by detecting the IR absorptions in a linear action regime by photodissociation of weakly bound N2 molecules, which are attached to the target ions in a cryogenically cooled, rf ion trap. We consider the specific case of the widely used drug Valsartan and two isomeric forms of its metabolite. Advantages and challenges of the cold ion approach are discussed, including disentangling the role of conformers and the strategic choices involved in the selection of the charging mechanism that optimize spectral differentiation among candidate structural isomers. In this case, the Na+ complexes are observed to yield sharp resonances in the high frequency NH and OH stretching regions, which can be used to easily differentiate between two isomers of the metabolite.

Graphical Abstract


Vibrational spectroscopy Mass spectrometry IR-spectroscopy Metabolomics Metabolite Drug discovery Conformer differentiation 



M.A.J. thanks the National Science Foundation for support under grant number CHE-1465100. This work was supported in part by the Yale University Faculty of Arts and Sciences High Performance Computing Facility (and staff). A.B. acknowledges financial support from the National Science Foundation through the HBCU-UP award no. 1505095. We also thank Nan Yang and Chinh Duong for their work on the updated instrumental capabilities utilized in this experiment (Figure 2).

Supplementary material

13361_2017_1767_MOESM1_ESM.pdf (10.2 mb)
ESM 1 (PDF 10398 kb)


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Copyright information

© American Society for Mass Spectrometry 2017

Authors and Affiliations

  • Olga Gorlova
    • 1
  • Sean M. Colvin
    • 1
  • Antonio Brathwaite
    • 2
  • Fabian S. Menges
    • 1
  • Stephanie M. Craig
    • 1
  • Scott J. Miller
    • 1
  • Mark A. Johnson
    • 1
  1. 1.Department of ChemistryYale UniversityNew HavenUSA
  2. 2.College of Science and MathematicsUniversity of the Virgin IslandsSt. ThomasVirgin Islands (U.S.)

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