Mitoxantrone Stability in Syringes and Glass Vials and Evaluation of Chemical Contamination

ABSTRACT The stability of mitoxantrone hydrochloride solutions was evaluated over 42 days. Mitoxantrone solutions of 2 mg/mL were stored in multidose glass vials, and Monoject syringes at 4°C and 23PC. On days 0, 2, 5, 7, 9, 14, 20, 22, 27, 32 and 42, the mitoxantrone concentration was measured using a stability-indicating liquid chromatographic method. Colour pH, and physical inspection were also completed. On each study day, the concentrations of two chemicals (MBT and HMBT) reported to be leached from the rubber gaskets of some syringes and DEHP, reported to be leached from PVC containers, were also measured. During the 42-day study period all solutions stored at either 4°C or 23°C retained more than 90% of the initial mitoxantrone hydrochloride concentration. All solutions remained clear and had no change in UV-VIS spectrum absorbance or pH. On day 42, mass balance indicated that less than 3% of the mitoxantrone had degraded. The MBT, HMBT and DEHP concentrations were below detectable limits (100, 100 and 200 ng/mL respectively) in all solutions. We conclude that mitoxantrone solutions (2 mg/mL) stored at 4°C or 23°C in the original glass vial are stable for 42 days. Since investigations have failed to demonstrate contamination of these solutions stored in Monoject ® syringes, we conclude that mitoxantrone solutions are also stable when stored at 4°C or 23°C in these syringes, and maintain acceptable product purity. RESUME La stabilite des solution de chlorhydrate de mitoxantrone a ete evaluee sur une periode de 42 jours. Les solutions de mitoxantrone (2 mg/mL) ont ete entreposees dans des flacons de verre mutli-dose et dans des seringues Monject a 4°C et 23°C. Les concentrations de mitoxantrone ont ete mesurees pendant onze jours d’etudes differents en utilisant une methode de chromatographie liquide approuvee pour determine la stabilite. La couleur, le pH et l’analyse physique ont aussi ete verifies. A chaque jour de l’etude les concentrations de deux produits chimiques (MBT et HMBT) qui filtraient des joints de caoutchouc de quelques seringues et due DEHP (qui filtrait des contenants de chlorure de polyvinyle) ont ete mesurees. Pendant la periode d’etude de 42 jours, toutes les solutions entreposees soit a 4°C soit a 23°C ont retenu plus do 90% de la concentration initiale de chlorhydrate de mitoxantrone. Elles sont demeurees claires et sans aucun changement d’absorbance de spectre UV-VIS ou de pH. Au jour 42, la balance de masse indiquait qu’environ 3% de mitoxantrone s’etait degrade. Dans toutes les solutions les concentrations de MBT, HMBT, et DEHP etaient en dessous des limites decelables. Nous concluons donc que les solutions de mitoxantrone (2 mg/mL) entreposees a 4°C ou 23°C en flacons de verre originaux sont stables pendant 42 jours. Puisque les analyses n’ont pas reussies a demontrer que les solutions entreposees dans ces seringues a 4°C ou 23°C sont egalement stables et maintiennent une purete acceptable du produit.

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