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

Matthias D'Hondt UGent, Elien Vangheluwe UGent, Sylvia Van Dorpe UGent, Jente Boonen UGent, TIENEKE BAUTERS UGent, BRIGITTE PELFRENE UGent, JOHAN VANDENBROUCKE UGent, Hugo Robays UGent and Bart De Spiegeleer UGent (2012) AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY. 69(3). p.232-240
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
Chromatography, Antineoplastic agents, 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
journal title
AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
Am. J. Health-Syst. Pharm.
volume
69
issue
3
pages
232 - 240
Web of Science type
Article
Web of Science id
000304123400014
JCR category
PHARMACOLOGY & PHARMACY
JCR impact factor
1.984 (2012)
JCR rank
153/259 (2012)
JCR quartile
3 (2012)
ISSN
1079-2082
DOI
10.2146/ajhp110208
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2023555
handle
http://hdl.handle.net/1854/LU-2023555
date created
2012-02-08 11:34:58
date last changed
2012-09-12 11:44:30
@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      = {Chromatography,Antineoplastic agents,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},
}

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.