Identification of conjugated metabolites of pyrazolone drugs in human urine by pyrolysis-mass spectrometry

It is shown that a combination of pyrolysis electron ionization and soft ionization mass spectrometry represents a direct approach for the elucidation of the complex biotransformation pattern of two pyrazolone analgesics, antipyrine and dipyrone. In a first screening procedure crude extracts from biological material can readily be utilized. Urinary conjugates of structural hydroxy isomers formed from antipyrine can be differentiated by specific thermolytic reactions of the pyrazolone moiety. As a rule, sulpho conjugates are found to exhibit a lower stability against thermal stress than the corresponding gluco conjugates. Using this integrated mass spectrometric approach, investigation of the phase II metabolism of dipyrone succeeded in identifying five unknown metabolites.