Identification of unknown degradation products in a new cholesterol-reducing drug by ion-chromatography coupled to mass spectrometry

The combination of suppressed and non-suppressed cation-exchange chromatography with electrospray ionization mass spectrometry was demonstrated for the structural elucidation of unknown by-products (mostly quaternary ammonium compounds) in a new cholesterol-reducing drug. The suppressed mode using methanesulfonic acid and acetonitrile turned out to be unsuitable because of regenerant (tetrabutylammonium hydroxide) passing through the membrane of the suppressor into the eluent which led to a significant increase of spectral background in the mass spectrometer. Employing a mobile phase consisting of 200 mM formic acid and 60% (v/v) acetonitrile, the separation and detection of 8 unknown compounds was possible in the non-suppressed mode. The three most prominent compounds were selected for structural elucidation utilizing collision induced dissociation experiments. In a series of experiments the fragmentation behavior was investigated for different fragmentation voltages finally leading to structure proposals. Using gas chromatography hyphenated with mass spectrometry, additional information for the structure of the unknowns was collected and a possible way of their formation was proposed. (C) 2001 Elsevier Science B.V. All rights reserved.