Application of LC-NMR and LC-MS to the identification of degradation products of a protease inhibitor in dosage formulations

LC-NMR and LC-MS were applied to the characterization of six degradation products of a protease inhibitor, N-hydroxy-1,3-di-[4-ethoxybenzenesulphonyl]-5,5-dimethyl-[1,3]cyclohexyldiazine-2-carboxamide, in a dosage formulation. A reversed-phase HPLC method was developed for the separation of the parent compound and its six degradation products. LC-MS was then utilized to obtain the molecular weight and fragmentation information using an electrospray ionization (ESI) interface in the positive ion mode. LC-NMR was employed to acquire detailed structural information using a selective solvent suppression pulse sequence in the stop-flow mode. This work demonstrated the usefulness of this integrated approach for the rapid and unambiguous identification of drug compounds and their degradation products in dosage formulations. (C) 1999 Elsevier Science B.V. All rights reserved.