INVESTIGATION OF THE METABOLISM OF EBROTIDINE IN HUMAN URINE BY LIQUID CHROMATOGRAPHY-ATMOSPHERIC PRESSURE CHEMICAL-IONIZATION MASS-SPECTROMETRY

Ebrotidine is a new H-2-receptor antagonist that, in addition to its a ntisecretory activity, exhibits a remarkable ability for gastric mucos al protection and acts as a potent inhibitor of protease and lipase en zymes elaborated by Helicobacter pylori. To study the metabolism of eb rotidine in human urine, HPLC/MS with an atmospheric pressure chemical ionization (APCI) interface and simultaneous UV detection was conduct ed. HPLC/MS separation of the reference compounds was performed, and p ositive and negative APCI mass spectra were obtained. Compounds of low molecular weight (M(r) < 300) showed predominantly the quasi-molecula r ion. Intermediate size compounds (300 < M(r) < 400) gave a different type of spectra, depending on the ion mode: the positive mass spectra showed only the protonated molecular ion, whereas in the negative mas s spectra many fragments appeared in addition to the deprotonated mole cular ion. For molecules with a higher molecular weight (M(r) > 400), high fragmentation was observed. LC/MS with an APCI interface in posit ive and negative modes allowed the identification of ebrotidine, 4-bro mobenzenesulfonamide, and four S-oxidized metabolites in human urine.