Journal of the American Society for Mass Spectrometry

, Volume 20, Issue 11, pp 2034–2048

Unusual mass spectrometric dissociation pathway of protonated isoquinoline-3-carboxamides due to multiple reversible water adduct formation in the gas phase

  • Simon Beuck
  • Tobias Schwabe
  • Stefan Grimme
  • Nils Schlörer
  • Matthias Kamber
  • Wilhelm Schänzer
  • Mario Thevis
Article

DOI: 10.1016/j.jasms.2009.07.016

Cite this article as:
Beuck, S., Schwabe, T., Grimme, S. et al. J Am Soc Mass Spectrom (2009) 20: 2034. doi:10.1016/j.jasms.2009.07.016

Abstract

The study of the collision-induced dissociation behavior of various substituted isoquinoline-3-carboxamides, which are amongst a group of drug candidates for the treatment of anemic disorders (e.g., FG-2216), allowed for the formulation of the general mechanisms underlying the unusual fragmentation behavior of this class of compounds. Characterization was achieved with high-resolution/high accuracy LTQ-Orbitrap tandem mass spectrometry of the protonated precursor ions. Presented data were substantiated by the synthesis and analysis of proposed gas-phase intermediate structures and stable isotope labeled analogues, as well as by density functional theory calculations. Exemplary, CID of protonated N-[(1-chloro-4-hydroxy-7-isopropoxy-isoquinolin-3-yl)carbonyl]glycine gives rise to the isoquinoline-3-carboxy-methyleneamide product ion which nominally eliminates a fragment of 11 u. This was attributed to the loss of methyleneamine (−29 u) and a concomitant spontaneous and reversible water addition (+18 u) to the resulting acylium ion to yield the protonated isoquinoline-3-carboxylic acid. The same water addition pattern is observed after loss of propylene (−42 u). A further nominal loss of 10 u is explained by the elimination of carbon monoxide (−28 u) followed by another water adduct formation (+18 u) to yield the protonated 1-chloro-3,4,7-trihydroxy-isoquinoline. The source of the multiple gas-phase water addition remained unclear. This atypical fragmentation pattern proved to be highly characteristic for all studied and differentially substituted isoquinoline-3-carboxamides, and offers powerful analytical tools for the establishment of a LC/MS(/MS) based screening procedure for model HIF-stabilizers and their potential metabolites in clinical, forensic and sports drug testing.

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Copyright information

© American Society for Mass Spectrometry 2009

Authors and Affiliations

  • Simon Beuck
    • 1
  • Tobias Schwabe
    • 2
  • Stefan Grimme
    • 2
  • Nils Schlörer
    • 3
  • Matthias Kamber
    • 4
  • Wilhelm Schänzer
    • 1
  • Mario Thevis
    • 1
  1. 1.Center for Preventive Doping Research, Institute of BiochemistryGerman Sport University CologneCologneGermany
  2. 2.Organic Chemistry InstituteWestfälische Wilhelms-Universität MünsterMünsterGermany
  3. 3.Institute for Organic ChemistryUniversity of CologneCologneGermany
  4. 4.Antidoping SwitzerlandBerneSwitzerland

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