Physical and chemical stability of methotrexate sodium, cytarabine, and hydrocortisone sodium succinate in Elliott's B solution

The purpose of this study was to evaluate the physical and chemical stabilities of methotrexate 2 mg/mL (as the sodium salt), cytarabine 3 mg/mL, and hydrocortisone 2 mg/mL (as the sodium succinate) in Elliott's B solution, an artificial cerebrospinal fluid. Three test solutions of each drug in Elliott's B solution were packaged as 20 mL of solution in 30-mL glass vials and 20-mL plastic syringes and were stored at 4° and 23°C. Aliquots were removed for evaluation initially and after 12 hours, 24 hours, and 48 hours of storage. Physical stability was assessed visually and by measuring turbidity with a color-correcting turbidimeter and particle content with a light-obscuration particle sizer and counter. Chemical stability was determined by assaying in duplicate the concentration of each drug at each time-point. Stability-indicating high-performance liquid chromatographic assays specific to each drug entity were used in the testing. All of the test samples were clear with no precipitation throughout the study. Furthermore, there was no increase in measured turbidity or particle content. Methotrexate sodium and cytarabine were very stable, exhibiting little or no loss in any sample. Similarly, hydrocortisone sodium succinate was stable for 48 hours when stored at 4°C. However, hydrocortisone sodium succinate was less stable at 23°C, with unacceptable losses occurring after 24 hours.