These conditioning regimens prior to allogenic or autologous HSC transplantation are used to treat a large number of malignant diseases such as leukemia and some solid tumors, as well as genetic diseases such as immune deficiency syndromes [4–7]. Other combinations associate CYT387 molecular weight busulfan with thiotepa. More recently, less myoloablative
combinations with fludarabine (BuFlu) have shown efficacy while offering lower extrahematological toxicity [8, 9]. According to the Summary of Product Characteristics (SPC), Busulfan (Busilvex®) is WZB117 administered intravenously (IV) at a recommended dose of 0.8 mg/kg in adults and 0.8–1.2 mg/kg (depending on bodyweight) in pediatric patients . It is administered by means of a 2-h infusion every 6 h for 4 consecutive days (giving a total of 16 doses). Because of its highly predictable linear pharmacokinetics, once-daily administrations are under evaluation in adults . Busulfan is provided as a 6 mg/mL concentrate and once it has been reconstituted in the form of a SHP099 0.55 mg/mL solution, the stability data provided by Pierre Fabre Laboratories are 8 h at 20 ± 5 °C (room temperature [RT]) or 12 h at 2–8 °C followed by 3 h at RT. More recently, a German study reported a period of stability of 36 h at a temperature between 13 and 15 °C for the same solutions
diluted to a 0.5 mg/mL dose and prepared in polypropylene (PP) bags or glass bottles [11, 12]. Busulfan undergoes a hydrolysis phenomenon in aqueous media, giving rise to methanesulphonic acid and tetrahydrofuran
(THF) . A precipitation phenomenon was also identified during these studies . The short shelf life specified in the SPC combined with the administration regimen of every 6 h for 4 consecutive days poses organizational problems for chemotherapy preparation, particularly at the end of the week. The purpose of our study was to investigate the stability of busulfan injection solution (Busilvex®) diluted in 0.9 % sodium chloride (NaCl) to a concentration of 0.55 mg/mL (the recommended concentration for administration) in three different containers: PP syringes, polyvinyl many chloride (PVC) bags, and glass bottles, when stored at three different temperatures (2–8, 13–15, and 20 ± 5 °C). We monitored changes in the busulfan content of this solution, its pH, and its osmolality over time, and sought to understand the phenomena causing the busulfan content to decrease. 2 Materials and Methods 2.1 Materials and Reagents Busulfan (Fig. 1) (Fluka, Steinheim, Germany; purity ≥99 %) was used to produce the series of standard solutions for calibration and the quality controls. Diethyldithiocarbamate (Fig. 1) (Sigma-Aldrich, St Louis, MO, USA) was used to prepare the derivatization solution each day. The Busilvex® used for the preparations was supplied by Pierre Fabre Oncologie, Boulogne, France.