GAS-PHASE FRAGMENTATION STUDY OF TWO 1,5-BENZODIAZEPIN-2-ONE DERIVATIVES USING ELECTROSPRAY IONIZATION TANDEM MASS SPECTROMETRY

Abstract

The fragmentation patterns of two 3-hydroxy-4-phenyltetrahydro-1,5-benzodiazepin-2-ones I, II possessing the same backbone structure, were investigated using electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/ MS) techniques. A simple methodology, based on the use of ESI (positive ion mode) and by increasing the declustering potential in the atmospheric pressure/vacuum interface, collision induced dissociation (CID), was used to enhance the formation of the fragment ions. In general, the coumpound studied afforded, in the gas phase, both protonated and sodiated molecules. This led to the confirmation of the molecular masses and chemical structures of the studied compounds. Exact accurate masses were measured using a high-resolution ESI quadrupole orthogonal time-of-flight (QqToF)-MS/MS hybrid mass spectrometer instrument. The breakdown routes of the protonated molecules were rationalized by conducting low-energy collision CIDMS/MS analyses (product ion- and precursor ion scans) using a conventional quadrupole hexapole-quadrupole (QhQ) tandem mass spectrometer. All the observed major fragmentations for the two 1,5-benzodiazepines occurred in the saturated seven-membered ring containing the nitrogen atoms. These formed a multitude of product ions by different breakdown routes. All the major fragmentations involved cleavages of the N-1–C-2 and C-3– C-4 bonds. Reconfirmation of the various geneses of the product ions was achieved by conducting a series of precursor ion scans. ESI-MS and CID-MS/MS analyses have thus proven to be a specific and very sensitive method for the structural identification of these novel 1,5-benzodiazepine derivatives.