Background and importance Mitomycin C is used in different regimens for the treatment of bladder, anus and lung cancer. According to the data sheet, reconstitution of the vial should be carried out with water for preparation of injectables or with 20% dextrose. Despite this, sodium chloride solutions are commonly used for its administration. However, it is known that the stability of mitomycin C molecule is affected by the pH of the preparation as degradation increases with pH values <7. Sodium chloride solutions have an approximate pH of 5.4. There are no published data to support how pH affects mitomycin C stability in 0.9% sodium chloride solutions (NSS).
Aim and objectives To study the stability of mitomycin C in NSS under different pH conditions and storage temperatures.
Material and methods A stability study was carried out in eight NSS with a commonly used mitomycin C concentration of 0.12 mg/mL. Solutions were prepared in duplicate for each pH: 4.5, 5.5, 6 and 7. The pH was adjusted with sodium hydroxide or phosphoric acid. Four solutions were stored at room temperature and four at 5°C. Mitomycin C concentration was assessed at 0, 30, 60, 120 and 300 min and 24 hours by high performance liquid chromatography. The areas obtained were compared with the initial area (time 0 min) to calculate the remaining mitomycin C percentage. A 10% level of degradation is assumed as the limit in terms of stability.
Results Remaining mitomycin C percentages were calculated. Analysing the results at room temperature, the remaining mitomycin C percentages were 98.5% at 30 min; 97.2% at 60 min; 92.7% at 120 min; 89.3% at 300 min; and 88.4% at 1 hour at pH=7. Remaining percentages were 99.2%, 98.6%, 97.6%, 95.8% and 87.4%, respectively, at pH=6. Percentages were 98.9%, 98,2%, 96.6%, 93.5% and 87.3%, respectively, at pH=5.5. Percentages for pH=4.5 were 98.0%, 96.7%, 88.1%, 85.4% and 83.2%, respectively. The concentration of all solutions remained above 90% of the initial concentration after 1 hour, regardless of the pH value, in contrast with the values at 24 hours.
Analysing the concentrations at 5°C, the remaining mitomycin C percentages were 99.2%, 98.4%, 97.3%, 94.9% and 90.0% at pH=7. Remaining percentages were 99.5%, 99.2%, 98.6%, 97.4% and 94.0%, respectively, at pH=6. Percentages were 99.8%, 99.6%, 99.2%, 98.4% and 95.3%, respectively, at pH=5.5. Percentages for pH=4.5 were 99.8%, 99.7%, 99.3%, 98.5% and 93.1%, respectively, for each time studied. All solutions stored in the fridge were stable over the 24 hours of the study.
Conclusion and relevance We demonstrated that the stability of mitomycin C solutions decreased over time and with lower pH values in NSS. Furthermore, room temperature significantly affected mitomycin C stability. However, degradation was greatly reduced at 5°C, regardless of pH. This proves that mitomycin C solutions in NSS can be stored in the fridge for 24 hours.
References and/or acknowledgements No conflict of interest.
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