Photodegradation paths of cefotaxime

Abstract

The degradation kinetics of cefotaxime sodium salt in aqueous solution, under UV light at 254 nm, was investigated by HPLC and antibiotic activity. This degradation is the result of two competitive processes, an isomerization and a photolysis. This study is mostly about the isomerization step. The measured quantum yields for the cefotaxime to its anti-isomer and anti-isomer to cefotaxime isomerizations are, respectively, 0.10 and 0.12. A photostationary state characterized by an anti:syn ratio of 1.2 is obtained after 30min of irradiation. The competitive photolysis, which actually consists of at least two processes (one on the Δ3-cephem ring and the second on the methoxyimino group), leads to an intense yellowing of the solution corresponding to the destruction of the molecule. The comparative evolution of the absorption spectra, under irradiation at 254 nm, of cefotaxime, thiazoximic acid, and 7-aminocephalosporanic acid shows that it is the Δ3-cephem ring photolysis which gives the yellow color. The major conclusion of this work is to call attention to the photoisomerization step which leads efficiently to the inactive anti-isomer, without giving any visible notice of degradation. Such a process is to be expected in all antibiotics containing an alkoxyimino linkage on the C-7 substitution.