METABOLISM OF EBROTIDINE - A REVIEW

A hypothetical metabolic pathway for ebrotidine E)-[[2-[[[2-[(diaminom ethylene]amino]-4-thiazolyl] ]ethyl]amino]methylene-4-bromo-benzenesul fonamide, CAS 100981-43-9, FI-3542) has been proposed on the basis of previous data on the metabolism of other H-2-receptor antagonists as w ell as on in vitro degradation assays of ebrotidine, Its potential met abolites have been synthesized and characterized, and their presence i n human urine has been investigated by high-performance liquid chromat ography (HPLC). Analytical-scale HPLC allowed the identification of me tabolites by means of their retention time and UV spectrum, while semi preparative-scale HPLC allowed their identification through FT-IR and LH-NMRI Mass spectrometry using atmospheric pressure chemical ionizati on (APCI) and electrospray ionization (ESI) for HPLC-MS coupling allow ed the identification of all metabolites in human urine. The quantitat ive determination of ebrotidine and its derivatives has been performed according to a newly designed method which consisted of a liquid-liqu id extraction in a basic medium followed by reversed-phase HPLC with i on-pair formation. This method was sensitive, precise and no chromatog raphic interferences with other drugs which might be administered in c ombination with ebrotidine were observed. In order to elucidate the ex cretion of ebrotidine, the analytical method was applied to the analys is of the urine collected from 2 healthy volunteers 96 h after receivi ng 400 mg of ebrotidine.