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Unexpected benzimidazole ring formation from a quinoneimide species in the presence of ammonium acetate as supporting electrolyte used in the coupling of electrochemistry with mass spectrometry
Author(s) -
Bussy Ugo,
Jurva Ulrik,
Boisseau Renaud,
AndresenBergström Moa,
Silvestre Virginie,
Galland Nicolas,
Jacquemin Denis,
Boujtita Mohammed
Publication year - 2015
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.7122
Subject(s) - chemistry , ammonium acetate , electrolyte , mass spectrometry , electrochemistry , acebutolol , electrospray ionization , supporting electrolyte , tandem mass spectrometry , benzimidazole , inorganic chemistry , chromatography , high performance liquid chromatography , organic chemistry , electrode , medicine , blood pressure , radiology
Rationale Electrochemistry (EC) coupled to mass spectrometry (MS) has been used to study different phase‐I reactions. Despite of the versatility of EC/MS, the effect of the nature of the supporting electrolyte on the formation of oxidation products has seldom been discussed during EC/MS experiments. Here, we present a comparison of two different supporting electrolytes and their effect on the identification of unstable intermediate oxidation species is discussed. Methods The oxidation of acebutolol was performed with a coulometric cell in the presence of two supporting electrolytes namely ammonium acetate and lithium acetate. Ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry (UPLC/QTOFMS) using a binary gradient (water/acetonitrile) with positive electrospray ionization was used to identify the oxidation products in the presence and absence of glutathione. Chemical structure elucidations of the oxidation products were performed by high‐resolution mass spectrometry (HRMS) and were also supported by nuclear magnetic resonance (NMR) measurements. Results From the electrochemical study and HRMS measurements, we demonstrate that the quinoneimide species resulting from the oxidative hydrolyses of acebutolol gives a benzimidazole ring product in the presence of ammonium acetate. Through the example of the oxidation of acebutolol, a correlation between the supporting electrolyte nature and oxidation product formation was established. The obtained results were supported by quantum mechanical calculations. Conclusions We present here evidence of the side reactions induced by the presence of ammonia as supporting electrolyte during EC/MS measurements. Acebutolol was used as a model to postulate an uncommon and unexpected side reaction leading to benzimidazole ring formation. The findings may help to understand the identification of the intermediate species in the oxidative degradation process. Copyright © 2015 John Wiley & Sons, Ltd.