HIGH-RESOLUTION H-1-NMR SPECTROSCOPIC STUDIES OF THE METABOLISM AND EXCRETION OF AMPICILLIN IN RATS AND AMOXICILLIN IN RATS AND MAN

High resolution proton nuclear magnetic resonance (H-1 NMR) spectrosco py has been used to investigate the metabolism and urinary excretion o f the aminopenicillins, ampicillin and amoxycillin, in rats and of amo xycillin in man. H-1 NMR resonances of the aminopenicillins, together with those for their 5R, 6R and 5S, 6R penicilloic acids and diketopip erazine metabolites were detected, assigned and quantified in urine sa mples with the aid of spin-echo NMR techniques. The dimer of amoxycill in was detected in rat urine for the first time together with novel dr ug-related resonances assigned to amoxycillin carbamate. Quantitative H-1 NMR spectroscopic results were consistent with HPLC and microbiolo gical data considering that only single measurements were recorded. Du e to the short analysis time and simple sample preparation, NMR was pa rticularly useful for studying the metabolism of the aminopenicillins for which sample degradation poses analytical problems. The non-invasi ve character of H-1 NMR spectroscopic analysis of urine also provided unique information on a reversible reaction between amoxycillin and bi carbonate, an endogenous urinary metabolite.