Investigation of the metabolism of ebrotidine in human urine by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.

Ebrotidine is a new H2-receptor antagonist that, in addition to its antisecretory activity, exhibits a remarkable ability for gastric mucosal protection and acts as a potent inhibitor of protease and lipase enzymes elaborated by Helicobacter pylori. To study the metabolism of ebrotidine in human urine, HPLC/MS with an atmospheric pressure chemical ionization (APCI) interface and simultaneous UV detection was conducted. HPLC/MS separation of the reference compounds was performed, and positive and negative APCI mass spectra were obtained. Compounds of low molecular weight (M(r) < 300) showed predominantly the quasi-molecular 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 mass spectra many fragments appeared in addition to the deprotonated molecular ion. For molecules with a higher molecular weight (M(r) > 400), high fragmentation was observed. LC/MS with an APCI interface in positive and negative modes allowed the identification of ebrotidine, 4-bromobenzenesulfonamide, and four S-oxidized metabolites in human urine.