Qualitative analysis of potential metabolites and degradation products of a new antiinfective drug in rat urine, using HPLC with radiochemical detection and HPLC-mass spectrometry.
High-performance liquid chromatography (HPLC) was used in combination with radioactivity detection and mass spectrometry (MS) to elucidate the metabolic fate of GV104326, a novel tricyclic beta-lactam antibacterial agent. Metabolic profiles were obtained by analysis of rat urine samples collected after intravenous administration of the 14C-labelled drug at the dose of 50 mg kg-1 (12.95 MBq kg-1). Methods for solid-phase extraction from urine samples and for reversed-phase chromatographic separation of drug related material were developed. HPLC-MS was used to confirm that the parent compound corresponded to the principal peak in the chromatograms, and two minor peaks were identified as potential metabolites of GV104326. They were shown to be an open beta-lactam ring derivative (GV173923) and a dimeric compound (GV196359).
Glaxo Research Laboratories-Drug Metabolism Department, GLAXO S.p.A., Verona, Italy.
L
L
Iavarone
M
M
Scandola
F
F
Pugnaghi
P
P
Grossi
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D007769:Lactams; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet
D000900:Anti-Bacterial Agents; C086671:GV 104326; D007769:Lactams