Investigations on the Stability of Carboplatin Infusion Solutions

摘要

The stability of the carboplatin market drug products Ribocarbo and Ribocarbo-L in 0.9% sodium chloride or 5% glucose infusion solution was investigated by HPLC analysis using a Nucleosil-120-5-C18 column, an eluent consisting of methanol and an aqueous solution of H_2SO_4 (0.001 N with Na_2SO_4 (0.02M); 10:90 or 5:95(v/v), and UV detection. At room temperature, carboplatin is stable in 0.9% NaCl solution for 1 h only. During the following 168h, a 10% degradation to cisplatin and the intermediate diamminechloro[O~1 -1-carboxylato-1-carboxycyclobutane] platinum(II) takes place. This reaction is independent of the carboplatin concentration used. Under identical conditions in 5% glucose solution the carboplatin concentrations decrease during 72h by about 2-3% and by 5-6% after 168h of storage. At 4deg, a 10mg/ml solution is stable during the experiment, whereas from a 1 mg/ml carboplatin infusion, 2% of the drug are lost after day 7 and about 3% after day 28. Degradation products were unequivocally identified. The presence of highly toxic carboplatin hydrolysis products, however, could be excluded.