USE OF ELECTROSPRAY-IONIZATION AND NEUTRAL LOSS LIQUID-CHROMATOGRAPHY TANDEM MASS-SPECTROMETRY IN DRUG-METABOLISM STUDIES

The application of liquid chromatography/mass spectrometry (LC/MS) and LC/MS/MS with electrospray ionization to drug metabolism studies was investigated using S 9788 and various synthesized metabolic products as model compounds to assess the response characteristics with regard to compound lipophilicity and the influence of biological matrix components. The results obtained demonstrate the versatility of the electrospray ionization technique to analyse compounds of widely varying polarity and the power of MS/MS to identify unequivocally metabolic products. These techniques offer a very rapid screening procedure that can be used to identify metabolic products and thus provide important early metabolic information that can be used in the candidate drug selection programme. These procedures were then applied to an in,lipo study sample and, using neutral loss MS/MS, it was possible to detect metabolites of S 9788 directly from a crude biological matrix (bile) without prior extraction or chromatography to confirm positively the identity of five important metabolites of S 9788 in the rat.