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 Samples were withdrawn at t = 0 h, 3 h, 6 h, and 24 h. The analytical column was a Zorbax eclipse XDB-C18 (150 mm × 4.6 mm; 5 µm particle size).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.

Outcomes of a Undiluted, One-Bag Desensitization Protocol for Chemotherapeutic Agents

“…CBDCA stability seems to depend on concentration, 16 and previous research show that the stability of CBDCA solutions could not be guaranteed at a concentration of 0.02 mg/mL. 17 In addition, this one-bag protocol minimizes potential human errors associated with calculation for multiple dilutions, multiple-dose preparations, or administration of multiple bags (such as incorrect drug concentration, incorrect order of desensitization solutions, or incorrect rate of infusion due to multiple bags), which enhances patient safety. However, it should be noted that potential human error could also occur in this protocol when adjusting infusion rates.…”

“…CBDCA stability seems to depend on concentration, 16 and previous research show that the stability of CBDCA solutions could not be guaranteed at a concentration of 0.02 mg/mL. 17…”

Standards for practical intravenous rapid drug desensitization & delabeling: A WAO committee statement

“…[213][214][215][216] Remarkably, there have been recent efforts to design protocols based on the use of one bag alone, which could reduce complexity in preparing the drug, avoid using low concentrations that might affect drug stability, and reduce human errors. [213][214][215][216][217][218] However, there are still some methodological limitations to one-bag protocols that need to be addressed. Firstly, there is a lack of large series of well-characterized patients (including DPT to minimize false-positive diagnosis of allergy) using one-bag protocols and including enough numbers of severe reactors.…”

Current situation of carboplatin desensitisation protocols in the hospitals of Spain

“…Carboplatin stability seems to depend on concentration 7. Previous research showed that the stability of carboplatin solutions could not be guaranteed at a concentration of <0.2 mg/mL 8…”