Characterization of cisplatin degradation as affected by pH and light.

The stability of cisplatin in 0.9% sodium chloride solution was studied. Cisplatin was reconstituted with sterile water for injection to achieve a concentration of approximately 1 mg/mL in 0.9% sodium chloride solution. The solutions were placed in flexible polyvinyl chloride containers, clear and amber glass flasks, and plastic syringes and stored at 22-25 degrees C in the dark or exposed to measured amounts of light and assayed periodically for up to 96 days. The initial pH of some of the solutions was adjusted. The stability of cisplatin in the solutions was determined by measuring the concentrations of cisplatin, trichloroammineplatinate(II) (TCAP), and trans-dichlorodiammineplatinum(II) (transplatin) with high-performance liquid chromatography and by measuring solution pH. The effect of adding ethylene oxide and other materials was also determined. TCAP was identified as the predominant degradation product of cisplatin in all the solutions. The rate of degradation was dependent on pH: In the dark, about 0.04% and 0.21% of the cisplatin degraded to TCAP per week at pH 4.3 and 6.3, respectively. The presence of ethylene oxide accelerated cisplatin degradation. Degradation also occurred during exposure to short-wavelength (350-490-nm) visible light. Storage in amber glass flasks offered more protection than storage in clear flasks. Isomerization of cisplatin to transplatin was not observed. The major degradation product of cisplatin was trichloroammineplatinate(II). Solution pH was the predominant factor affecting cisplatin stability.