Stability of high dose melphalan in saline solution.

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Stability of high dose melphalan in saline solution

M.T. Baylatry, D. Geay, C. Guntz, J.L. Prugnaud, A.C. Joly
Saint-Antoine Hospital, Pharmacy, Paris Cedex 12, France

Background: Melphalan is an effective anticancer drug used in high doses as preparative regimen for haematopoietic stem cell transplantation (off-label indication). In Saint-Antoine hospital, melphalan concentration for chemotherapy infusion bag, in this indication, is between 0.8 mg/mL and 1.6 mg/mL. In melphalan
summary of product characteristics, the recommended maximum concentration is 0.45 mg/mL and the stability at this concentration in infusion bag is reported to be 90 min at room temperature. A chemical stability assay of high dose melphalan has been developed firstly to validate the safety of this unlicensed preparation and then to make possible melphalan centralized preparation and storage.

Methods: A liquid chromatographic UV method was used. The evaluation of stability (International Conference on Harmonization guidelines) and the accelerated degradation (temperature) were performed. The stability was established as the 95% of initial concentration. Melphalan solution in saline (0.9% NaCl) infusion bags were assessed at room temperature (average: 28°C) for 0.3 mg/mL (n=3) and 1.6 mg/mL (n=3) concentrations and at + 4°C for 0.8 mg/mL (n=3) and 1.6 mg/mL (n=3). Samples were collected at different times from 0h to 24h. Visible particulate formation or colour change were also evaluated.

Results: Melphalan solutions were degraded at room temperature within 2 hours (76% and 78% of initial concentration respectively for 0.3 mg/mL and 1.6 mg/mL). At + 4°C, melphalan concentrations (0.8 mg/mL and 1.6 mg/mL) remained above 95% for 3 hours. No color change or visible particulate formation were observed.

Conclusions: High dose melphalan is not degraded rapidly in saline solution. This study allows to prepare high dose melphalan infusion bags without recurring to high volumes of saline solution which may expose patients to hydric overload. The 3 hour stability of melphalan at + 4°C is compatible with an anticancer drug centralized preparation in Pharmacy department in order to avoid an extemporaneous preparation by nurses in Haematology department and improve their safety.

References: 14th Congress of EAHP. Barcelona. 2009