Long term stability study of cisplatin in polyolefin infusion bags in dose banding conditions using eco-friendly hydrophilic interaction chromatography and colorimetry methods
Yves Claude Guillaume, Lydie Lethier, Maurad Cabut, Cédric Peudepiece, Christine Fagnoni-Legat, Claire ANDREPurpose
The aim of this study was to develop and validate a green and sustainable hydrophilic interaction chromatography (HILIC) stability indicating assay for measuring the concentration of cisplatin and to evaluate its long-term stability at standardized rounded doses in polyolefin (POF) infusion bags at 25°C ± 3°C, 60% ± 5% relative humidity and protected from daylight. Physical stability, including colorimetry was periodically performed.
Methods
The HILIC with diode array detector method was fully validated and responds perfectly to degradation tests. Diluted cisplatin infusion solutions were aseptically prepared by further dilution of cisplatin stock solution with NaCl 0.9% in POF infusion bags (508 mL) at banded doses of 30 mg, 200 mg, and 400 mg. The POF bags were stored at 25°C in the dark. Physical and chemical stabilities were evaluated respectively through visual inspection, turbidity, particulate contamination, colorimetry measurements and through chromatographic assays, pH and osmolality monitoring.
Results
. The long-term stability of cisplatin was confirmed for at least 25 weeks at 25°C and in the dark. In addition, it was shown that a potential exposure of the cisplatin infusion bags in the natural light, the time to fall to 95% (90%) of the initial concentration would be estimated at eight (sixteen) minutes.
Conclusions
A simple, accurate, and eco-friendly stability-indicating HILIC method was developed to determine cisplatin concentrations in dose-banding conditions associated for the first time with color variation investigation. This study supports a centralized production of cis-platine in accordance with the studied conditions.