Stability of four standardized preparations of methotrexate, cytarabine, and hydrocortisone for intrathecal use

• Published in: Journal of oncology pharmacy practice 2016-10, Vol.22 (5), p.659-665
• Main Authors: Olmos-Jiménez, Raquel, Espuny-Miró, Alberto, Díaz-Carrasco, María Sacramento, Fernández-Varón, Emilio, Valderrey-Pulido, Manuel, Cárceles-Rodríguez, Carlos
• Format: Article
• Language: English
• Subjects: Chromatography, High Pressure Liquid; Cytarabine - chemistry; Drug Compounding - standards; Drug Stability; Humans; Hydrocortisone - analogs & derivatives; Hydrocortisone - chemistry; Hydrogen-Ion Concentration; Injections, Spinal; Methotrexate - chemistry; Osmolar Concentration; Temperature
• ISSN: 1078-1552; 1477-092X
• DOI: 10.1177/1078155215600905

Introduction Intrathecal administration of methotrexate, cytarabine, and hydrocortisone is commonly used to treat and prevent central nervous system involvement in leukemias and lymphomas. The use of intrathecal solutions with pH and osmolarity values close to physiologic range of CSF (pH 7.31–7.37, osmolarity 281–306 mOsm/kg) and standardization of the methotrexate, cytarabine, and hydrocortisone doses in children and adults based on age is highly recommended. Stability studies of standardized intrathecal mixtures under these conditions have not yet been published. Objective The purpose of this study was to evaluate the physical and chemical stabilities of four standardized mixtures of methotrexate, cytarabine, and hydrocortisone stored at 2–8℃ and 25℃ up to 7 days after preparation. Methods Four different standardized intrathecal mixtures were prepared and stored at 2–8℃ and 25℃ and protected from light. Triplicate samples were taken at different times and precipitation, appearance, color, pH, and osmolarity were analyzed. Methotrexate, cytarabine, and hydrocortisone concentrations were measured using a modified high-performance liquid chromatography method. Results No variation greater than 10% of the initial concentration of methotrexate, cytarabine, and hydrocortisone was observed in any of the four standardized mixtures for the 7 days of study when stored at 2–8℃ and 25℃ and protected from light. The osmolarity of the four preparations was within the physiologic range of CSF for 7 days at both 2–8℃ and 25℃. The pH values close to the physiologic range of CSF were stable for 48 h at 25℃ and for 120 h at 2–8℃. Conclusions Triple intrathecal standardized preparations of methotrexate, cytarabine, and hydrocortisone sodium phosphate are physically and chemically stable at 25℃ for 48 h and at 2–8℃ for 5 days.