Thermal and alkaline stability of meropenem: Degradation products and cytotoxicity

The stability of the broad-spectrum antibiotic meropenem was investigated in order to isolate and elucidate the mean degradation products involved in thermal and alkaline decomposition of meropenem, in solution. The purification of thermal degradation product (45 degrees C) involved a combination of preparative chromatographic techniques. The degradates were characterized by NMR and ESI-MS. The thermal degradation product was a result of several chemical reactions, with modification of side chain and beta-lactam ring, resulting in a pyrrolic derivative. Under alkaline conditions (NaOH 0.1 N), meropenem was converted totally to the corresponding beta-lactam ring-opened derivative, in sodium salt state. The degraded samples of meropenem reconstituted solution, powder for injection and alkaline solution was also studied in order to determine the preliminary cytotoxicity in vitro against mononuclear cells. The results obtained indicated that samples could be toxic in high concentration (2.0 mg/mL) after 48 h of incubation. The present study confirms the lability of the drug in aqueous solution, specially when submitted to thermal and alkaline conditions. Thus, it is necessary attention during the handling and storage of this antibiotic. (c) 2007 Elsevier B.V. All rights reserved.