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Stability of extemporaneously prepared cytarabine, methotrexate sodium, and methylprednisolone sodium succinate

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Abstract
Purpose. The short-term stability of extemporaneously prepared triple intrathecal therapy, containing cytarabine, methotrexate sodium, and methylprednisolone sodium succinate, was evaluated. Methods. Three batches of triple intrathecal solution were prepared using commercially available products and stored in three different packaging materials (plastic syringe system, brown glass vials, and brown glass vials filled with metal needles). The solutions were protected from light and stored at 5 degrees C, 25 degrees C, and 40 degrees C or exposed to ultraviolet and visible light at 25 degrees C, compliant with the International Conference on Harmonisation. Samples were taken immediately before and after 4, 8, 24, 32, and 48 hours of storage. Simultaneous high-performance liquid chromatography-ultraviolet light/diode array detector assay of cytarabine, methotrexate sodium, and methylprednisolone sodium succinate was performed using a fused-core stationary phase and an acetonitrile-based gradient. First-order kinetic degradation values were calculated, and temperature dependence was evaluated using the Arrhenius equation. Results. Cytarabine was stable under all storage conditions. Methotrexate sodium displayed significant degradation after light exposure but remained stable under the other storage conditions. Methylprednisolone sodium succinate was found to be the most labile component in the triple intrathecal solution. Temperature-dependent degradation was observed, resulting in 46% degradation after 48 hours at 40 degrees C. Two degradants were formed: methylprednisolone and methylprednisolone hydrogen succinate. Packaging material and batch-to-batch variability did not significantly influence the stability of the triple intrathecal solution. Conclusion. Triple intrathecal solution of cytarabine, methotrexate sodium, and methylprednisolone sodium succinate was stable for up to 12 hours when stored at 5 degrees C and protected from light.
Keywords
Antineoplastic agents, Chromatography, liquid, Compounding, Containers, Contamination, Cytarabine, Glass, Injections, Methotrexate sodium, Methylprednisolone, Methylprednisolone hydrogen succinate, Methylprednisolone sodium succinate, Photodecomposition, Plastics, Stability, Steroids, cortico, Storage, Temperature, INTRATHECAL METHOTREXATE, MENINGEAL LEUKEMIA, COMPATIBILITY, THERAPY, DRUGS

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Chicago
D’Hondt, Matthias, Elien Vangheluwe, Sylvia Van Dorpe, Jente Boonen, Tieneke Bauters, BRIGITTE PELFRENE, Johan Vandenbroucke, Hugo Robays, and Bart De Spiegeleer. 2012. “Stability of Extemporaneously Prepared Cytarabine, Methotrexate Sodium, and Methylprednisolone Sodium Succinate.” American Journal of Health-system Pharmacy 69 (3): 232–240.
APA
D’Hondt, Matthias, Vangheluwe, E., Van Dorpe, S., Boonen, J., Bauters, T., PELFRENE, B., Vandenbroucke, J., et al. (2012). Stability of extemporaneously prepared cytarabine, methotrexate sodium, and methylprednisolone sodium succinate. AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY, 69(3), 232–240.
Vancouver
1.
D’Hondt M, Vangheluwe E, Van Dorpe S, Boonen J, Bauters T, PELFRENE B, et al. Stability of extemporaneously prepared cytarabine, methotrexate sodium, and methylprednisolone sodium succinate. AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY. 2012;69(3):232–40.
MLA
D’Hondt, Matthias, Elien Vangheluwe, Sylvia Van Dorpe, et al. “Stability of Extemporaneously Prepared Cytarabine, Methotrexate Sodium, and Methylprednisolone Sodium Succinate.” AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY 69.3 (2012): 232–240. Print.
@article{2023555,
  abstract     = {Purpose. The short-term stability of extemporaneously prepared triple intrathecal therapy, containing cytarabine, methotrexate sodium, and methylprednisolone sodium succinate, was evaluated. 
Methods. Three batches of triple intrathecal solution were prepared using commercially available products and stored in three different packaging materials (plastic syringe system, brown glass vials, and brown glass vials filled with metal needles). The solutions were protected from light and stored at 5 degrees C, 25 degrees C, and 40 degrees C or exposed to ultraviolet and visible light at 25 degrees C, compliant with the International Conference on Harmonisation. Samples were taken immediately before and after 4, 8, 24, 32, and 48 hours of storage. Simultaneous high-performance liquid chromatography-ultraviolet light/diode array detector assay of cytarabine, methotrexate sodium, and methylprednisolone sodium succinate was performed using a fused-core stationary phase and an acetonitrile-based gradient. First-order kinetic degradation values were calculated, and temperature dependence was evaluated using the Arrhenius equation. 
Results. Cytarabine was stable under all storage conditions. Methotrexate sodium displayed significant degradation after light exposure but remained stable under the other storage conditions. Methylprednisolone sodium succinate was found to be the most labile component in the triple intrathecal solution. Temperature-dependent degradation was observed, resulting in 46\% degradation after 48 hours at 40 degrees C. Two degradants were formed: methylprednisolone and methylprednisolone hydrogen succinate. Packaging material and batch-to-batch variability did not significantly influence the stability of the triple intrathecal solution. 
Conclusion. Triple intrathecal solution of cytarabine, methotrexate sodium, and methylprednisolone sodium succinate was stable for up to 12 hours when stored at 5 degrees C and protected from light.},
  author       = {D'Hondt, Matthias and Vangheluwe, Elien and Van Dorpe, Sylvia and Boonen, Jente and Bauters, Tieneke and PELFRENE, BRIGITTE and Vandenbroucke, Johan and Robays, Hugo and De Spiegeleer, Bart},
  issn         = {1079-2082},
  journal      = {AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY},
  keyword      = {Antineoplastic agents,Chromatography,liquid,Compounding,Containers,Contamination,Cytarabine,Glass,Injections,Methotrexate sodium,Methylprednisolone,Methylprednisolone hydrogen succinate,Methylprednisolone sodium succinate,Photodecomposition,Plastics,Stability,Steroids,cortico,Storage,Temperature,INTRATHECAL METHOTREXATE,MENINGEAL LEUKEMIA,COMPATIBILITY,THERAPY,DRUGS},
  language     = {eng},
  number       = {3},
  pages        = {232--240},
  title        = {Stability of extemporaneously prepared cytarabine, methotrexate sodium, and methylprednisolone sodium succinate},
  url          = {http://dx.doi.org/10.2146/ajhp110208},
  volume       = {69},
  year         = {2012},
}

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