Physicochemical stability of lurbinectedin reconstituted at 500 μg/mL and diluted at 15, 30, and 70 μg/mL in 0.9% sodium chloride and 5% dextrose

Abstract

Abstract Background: Lurbinectedin (ZEPZELCA) is a cytotoxic, with alkylating properties. The commercially available pharmaceutical form is a glass vial containing 4 mg of lyophilized powder of lurbinectedin. The recommended dose of lurbinectedin is 3.2 mg/m2. For a 1.7-m2 body surface area, the average dosage is 5.44 mg. The manufacturer indicates a 30-hour stability for the reconstituted solution which cannot give the possibility to re-use the vial for the following days resulting in an average loss of 3600 € per preparation. Objectives: The first objective was to study the stability of 500 μg/mL reconstituted lurbinectedin in water for injection after storage at 2 to 8°C. The second objective was to study the stability of 15 to 70 μg/mL diluted lurbinectedin in 0.9% NaCl or dextrose 5% in water stored at 2 to 8°C. Methods: Three solutions in glass tubes for each condition (reconstituted 15 and 70 μg/mL solutions) were prepared. Due to the high cost, only 1 infusion bag at 30 μg/mL in polyolefin container was prepared. At each time of the analysis, 3 samples for each vial were analyzed by high-performance liquid chromatography coupled to a photodiode array detector. Physical stability was evaluated by visual and subvisual inspection (spectrophotometry). Results: The analytical method was validated according to International Conference on Harmonisation guidelines Q2 (R1). The 500 μg/mL lurbinectedin reconstituted solution retained more than 95% of the initial concentration after 14 days as the 15 to 70 μg/mL diluted solutions. No interaction between the polyolefin infusion bag and lurbinectedin was observed. No physical changes were observed both visually and subvisually. Conclusion: The reconstituted solution and the diluted lurbinectedin solutions were physically and chemically stable for 14 days when stored at 2 to 8°C protected from light. This new data makes it possible to re-use the reconstituted vial and to store a preparation in case of cancellation of an administration.