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 chromatogr aphy with electrospray ionization mass spectrometry was demonstrated for th e structural elucidation of unknown by-products (mostly quaternary ammonium compounds) in a new cholesterol-reducing drug. The suppressed mode using m ethanesulfonic 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 spect ral background in the mass spectrometer. Employing a mobile phase consistin g of 200 mM formic acid and 60% (v/v) acetonitrile, the separation and dete ction of 8 unknown compounds was possible in the non-suppressed mode. The t hree most prominent compounds were selected for structural elucidation util izing collision induced dissociation experiments. In a series of experiment s the fragmentation behavior was investigated for different fragmentation v oltages finally leading to structure proposals. Using gas chromatography hy phenated with mass spectrometry, additional information for the structure o f the unknowns was collected and a possible way of their formation was prop osed. (C) 2001 Elsevier Science B.V. All rights reserved.