Amoxycillin dimerization

Nuclear magnetic resonance (NMR) spectroscopy of untreated biological fluids has been used successfully in metabolic studies of penicillins. Connor et al. [153] used this method to investigate the metabolism and urinary excretion of ampicillin and amoxycillin in humans and rats. In addition to the metabolites 5.49 and 5.50, they detected a dimer of amoxycillin (5.51) in rat urine. 

H. Bundgaard, Polymerization of penicillins. II. Kinetics and mechanism of dimerization and self-catalyzed hydrolysis of amoxycillin in aqueous solution, Acta Pharm. Suec. 14, 47-66 (1977). 

Everett et al. first reported the application of NMR spectroscopy in metabolism studies. In 1984, they studied the metabolites of ampicillin in rats using spin-echo H NMR spectroscopy [4]. Apart from the unchanged penicillin, the natural (5R)-isomer of penicilloic acid, the epimerized (55)-isomer as well as a new metabolite, a diketopiperazine derivative, were identified in urine. Reinvestigation of ampicillin and corresponding penicillins ten years later confirmed the results in the case of amoxycillin, a dimeric metabolite was additionally found [5]. 

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