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J Am Soc Mass Spectrom. 2017 Nov;28(11):2414-2422. doi: 10.1007/s13361-017-1767-z. Epub 2017 Aug 11.

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

Author information

1
Department of Chemistry, Yale University, New Haven, CT, 06520, USA.
2
College of Science and Mathematics, University of the Virgin Islands, St. Thomas, 00802, Virgin Islands (U.S.).
3
Department of Chemistry, Yale University, New Haven, CT, 06520, USA. mark.johnson@yale.edu.

Abstract

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 ᅟ.

KEYWORDS:

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

PMID:
28801884
DOI:
10.1007/s13361-017-1767-z

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