Stability of carboplatin infusion solutions used in desensitization protocol

Abstract

Carboplatin hypersensitivity reactions are one of the major clinical challenges in treating patients with relapse/recurrent ovarian malignancies. Desensitization protocols allow the continuation of treatment in patients who have presented hypersensitivity reactions by gradually re-introducing small amounts of the drug up to full therapeutic doses. Carboplatin desensitization protocol is based on three solutions that are usually prepared in the chemotherapy centralized units of hospital pharmacies. First and second solutions are diluted under the established concentration limit to guarantee the stability of the preparation. We developed a specific high-performance liquid chromatography assay to determine the stability of carboplatin infusion solutions that have been diluted to 0.2 mg/mL and 0.02 mg/mL in 250 mL of 5% dextrose in polypropylene infusion bags which were stored 24 h protected from light at room temperature. Samples were withdrawn at t ¼ 0 h, 3 h, 6 h, and 24 h. The analytical column was a Zorbax eclipse XDB-C18 (150 mm 4.6 mm; 5 mm particle size). The mobile phase had a flow rate of 1 mL/min under isocratic conditions of water–methanol (98:2, v/v). For 0.2 mg/mL solution, the high-performance liquid chromatography assay revealed no significant losses in carboplatin concentration. However, in 0.02 mg/mL solution remaining carboplatin was > 105% the initial dose after 3 h of storage at room temperature. The ultraviolet–visible spectra analysis showed that carboplatin remained intact during the study in 0.2 mg/mL solution, but some changes were detected in 0.02 mg/mL solution. Thus, 0.2 mg/mL carboplatin solution is stable for 24 h at room temperature in 5% dextrose polypropylene infusion bags but stability could not be proved for 0.02 mg/mL solution.