Stability of cytarabine, methotrexate sodium, and hydrocortisone sodium succinate admixtures

A high-performance liquid chromatographic (HPLC) method was developed for simultaneous determination of cytarabine, methotrexate sodium, and hydrocortisone sodium succinate, and the stability of the three drugs mixed together in four infusion fluids was assessed. Solutions were prepared with two concentrations of the three drugs similar to those administered intrathecally. Admixtures were prepared in Elliott's B solution, 0.9% sodium chloride injection, 5% dextrose injection, and lactated Ringer's injection. and lactated Ringer's injection. Solutions were filtered and kept in a disposable syringe in a 25 degrees C water bath for 24 hours. An HPLC assay capable of separating the three drugs and their degradation products was developed and validated. With one exception, all three drugs were stable in all four solutions for 24 hours. Hydrocortisone sodium succinate concentrations decreased to less than 90% of initial concentration in one of the admixtures with Elliott's B solution. No precipitation was noted in any admixture during the first eight hours of storage, but longer storage led to precipitation of unknown substances in some solutions. Admixtures of these three drugs in the four solutions tested are stable for at least 10 hours at 25 degrees C. However, intrathecal and administration of such admixtures within several hours of preparation is encouraged since none contains antibacterial preservatives.