Time-Dependent Degradation of Imipenem in Aqueous Solution and Its Impact on Antibacterial Activity.

Background/

Objectives

Imipenem, known as a carbapenem, is widely used in combination with Cilastatin to treat severe bacterial infections. Imipenem is a β-lactam antibiotic with potent antibacterial activity but a relatively unstable chemical structure. Due to these structural characteristics, it may degrade or undergo structural changes over time in aqueous solutions.

Methods

In this study, Imipenem was investigated for its structural stability over time in aqueous solution at 37 °C. Structural changes in the Imipenem/Cilastatin solution were confirmed by HPLC-DAD at the maximum absorbance wavelength.

Results

Imipenem undergone progressive degradation and structural transformation for the dimerization, while Cilastatin remained stable under the same conditions. LC-Q-TOF/MS confirmed the formation of a dimeric Imipenem species after prolonged incubation. Antibacterial activity showed that Imipenem was effective against P. carotovorum regardless of the dissolution times. However, Imipenem solution after 24 h with chemical degradation exhibited significantly decreased effects against E. coli and P. aeruginosa.

Conclusions

Accordingly, the patterns of metabolite changes in Imipenem and Cilastatin were characterized according to concentration and dissolution time, and the corresponding antibacterial activities against different bacterial strains were compared.