4 Discussion Our study data differ somewhat from other reports on the stability of busulfan solutions. The divergences observed between the different studies can be partly explained by non-identical study conditions and parameters. Indeed, whereas Pierre Fabre Laboratories who market Busilvex® recommend a shelf-life in PP syringes or in PVC bags of 12 h at 2–8 °C followed by 3 h at RT [3], the study by Karstens and Krämer [11] found a greater period

of stability (19 h) at the same temperature in syringes. Indeed, the study conducted DAPT by the manufacturer made its conclusions on the basis of a 5 % threshold, whereas the German study, conducted in a hospital environment, used a 10 % specification threshold for refrigerated storage only. Comparing the three containers evaluated in this study, our results demonstrate that the PP syringe offers the best storage regardless of temperature. This is in contrast to the results of the German study, which demonstrated that glass is more suitable, giving 48 or 36 h of stability depending on the storage temperature. Senoo and www.selleckchem.com/products/apr-246-prima-1met.html co-workers [15] also demonstrated that colourless PP syringes offered good stability for busulfan, with their data indicating that under refrigeration, busulfan solution was physically and chemically stable for up to 96 h. Other storage containers are available, including polyolefin/polyamide laminate packs. A recent study evaluated

the stability of busulfan solutions when stored in such packs. Busulfan solutions were prepared in physiological saline at

0.24 mg/mL click here and at 0.12 mg/mL and stored under refrigeration or at RT [16]. Regardless of the drug concentration or storage conditions, there was less than 90 % of the starting concentration remaining after 24 h. Another divergence in results relates to the storage temperature. Whereas the SPC indicates that the period of stability decreases if the temperature increases, the German study surprisingly observed stability for up to 36 h at 13–15 °C and lower stability, 19 h, at 2–8 °C. out Our results indicate that there is a decrease in stability with an increase in storage temperature; based on a 10 % threshold, stability in PP syringes was 24 h at 2–8 °C, 8 h at 13–15 °C, and 8 h at RT. In the study evaluating the polyolefin/polyamide bags, a lower storage temperature was also associated with better stability, at least for the 0.24 mg/mL solution (16.7 h at 4 °C vs. 8.4 h at RT) [16]. Interestingly, the stability of the 0.12 mg/mL solution was largely independent of storage temperature (11.5 h at 4 °C vs. 12.0 h at RT). The second part of our study was an attempt to explain the reduction in busulfan content on storage. It is well known that busulfan is only slightly soluble in water, which justifies the presence of the solvent DMA in the composition of the pharmaceutical product.