Stability study of a 10 mg/ml concentrated solution of doxorubicin

M. Boutet1, T. Briot1,2, S. Vrignaud1, F. Lagarce1,2 1 CHU Angers, service pharmacie, Angers, France
2 L’université Nantes Angers Le Mans, INSERM U1066, Micro et nanomédecines biomimétiques,
Angers, France

For the intermediate stage of the hepatocellular carcinoma, the chemoembolization (CEL) procedure is the recommended first line treatment. It combines an anthracycline and Lipiodol®.
Doxorubicin is the most commonly used anthracycline.
Only the stability of the 2 mg/ml doxorubicin is described while a more concentrated solution would reduce the injected volume, therefore the patient’s pain.
The aim of this study was to evaluate the stability of a 10 mg/ml doxorubicin solution.

Doxorubicin hydrochloride (Adriblastine®) was reconstituted in sodium chloride at a concentration of 10 mg/ml and stored in polypropylene syringes or glass vials, at 4-8°C, protected from light.
A stability indicating method was developed, according to ICH and the GERPAC methodological guideline stability studies.
Doxorubicin concentration was followed over 22 days with a high performance liquid chromatography, coupled with a diode array detector.
The spectrum was scanned from 190 to 700 nm and quantification, carried out at 254 nm (n=3).
Forced degradation was obtained by the addition of 0.01M NaOH.

Doxorubicin relative concentrations were systematically greater than 90% of the initial concentration : 97.0 +/- 0.3% at D22 for the glass vials, 95.1 +/- 1.0% at D22 for syringes.
No degradation products were observed on chromatograms and spectra obtained were all strictly similar to that of the original solution.
No color change and no precipitation were observed.

At 10 mg/ml, in polypropylene syringes or glass vials, protected from light and between 4 and 8°C, doxorubicin solution is stable 22 days.
This preparation is now used in our hospital to reduce the CEL volume.
No microbiological testing was performed because doxorubicin was reconstituted in controlled atmosphere zone ISO 5 class.

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