Background In the hospital setting, commercially available multi-dose formulations in solution are more practical but also more expensive in comparison with products reconstituted on site.
In Italy, cyclophosphamide (CP) is sold by Baxter as a galenic solution with 40 day stability at 2–8°C, including 12 days for microbial release, using safe compounding practices. Reconstitution of lyophilised Endoxan (also sold by Baxter) in saline solution is less practical but lower in cost. Its use is recommended within 2–3 h from preparation.
Purpose To evaluate the stability of Baxter solution formulations of CP after 12 days (common delivery time to hospital) and 40 days from the preparation date and to compare with the stability profile of reconstituted saline solutions of solid CP (Endoxan), under the same storage temperature (2–8°C).
Material and methods Analyses were performed directly on saline formulations without any pretreatment, under controlled temperature and using a high resolution nuclear magnetic resonance spectrometer (600 MHz).
Results After 12 days from preparation of Endoxan (4°C), about 0.5% of degradation compounds were present with an increase to approximately 2% after 40 days (4°C). For the Baxter formulation, more than 2% of degradation products were present after 12 days with an increase to 6% after 40 days. Traces of ε-caprolactam were detected in the Baxter formulations as well as in the Baxter saline solution, although this compound does not seem to interfere with the degradation pathways.
Conclusion Stability of CP is highly dependent on storage conditions (cold chain from factory to hospital). This can be better controlled for in laboratory reconstituted lyophilised Endoxan than in multi-dose formulations that need logistic support. To achieve the best quality therapy, the results support the reconstitution procedure as opposed to the use of pre-made formulations, even if the compounding procedures are less safe. Finally, the use of Endoxan offers a cost benefit. Nuclear magnetic resonance demonstrates its potential as a quantitative and non-invasive technique for detecting degradation products and eventual contaminants. Its use could also support the hospital pharmacy in terms of safety.
No conflict of interest.
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