Investigations on the stability of carboplatin infusion solutions

The stability of the carboplatin market drug products Ribocarbo(R) and Ribo carbo-L(R) in 0.9% sodium chloride or 5% glucose infusion solution was inve stigated by HPLC analysis using a Nucleosil-120-5- C18 column, an eluent co nsisting of methanol and an aqueous solution of H2SO4 (0.001 N with Na2SO4 (0.02 M); 10:90 or 5:95 (v/v)), and UV detection. At room temperature, carboplatin is stable in 0.9% NaCl solution for 1 h on ly. During the following 168 h, a 10% degradation to cisplatin and the inte rmediate 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 concentra tions decrease during 72 h by about 2-3% and by 5-6% after 168 h of storage . At 4 degrees C, a 10 mg/ml solution is stable during the experiment, wher eas 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 identi fied. The presence of highly toxic carboplatin hydrolysis products, however , could be excluded.