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Short-term storage stability of Triple IT solution

Matthias D'Hondt, Elien Vangheluwe UGent, Nadia Lemeire UGent, Tieneke Bauters, BRIGITTE PELFRENE, Johan Vandenbroucke, Hugo Robays UGent and Bart De Spiegeleer UGent (2011) Abstract book 15th forum of pharmaceutical sciences.
abstract
For the majority of children with acute lymphoblastic leukemia (ALL), treatment consists in part of a triple intrathecal (Triple IT) therapy, i.e. a combination of cytarabine (CB), methotrexate (MT) and methylprednisolone sodium succinate (MPSS) [1]. This combination product is prepared ex-tempore. However, no in-use shelf-life under defined storage conditions has yet been established. In this study, the short-term storage stability (up to 48 hours) was evaluated and included following study design variables: i) 3 packaging materials, i.e. PhaSeal® system, dark glass vial and dark glass vial + needles, ii) 4 storage conditions, i.e. light protected at 5 °C, 25 °C, 40 °C and photometric (UV and visible light) exposure at 25 °C, iii) batch reproducibility, i.e. 3 different batches. Calculation of the degradation kinetic parameters, obtained from HALO-HPLC-UV/DAD data, was performed using the Arrhenius equation to describe the temperature dependence. Moreover, identity of the major degradants was performed using ESI-MSn detection, and their specification relevance discussed. While CB is reasonably stable, MPSS did show hydrolysis as well as isomerisation (21- to 17-succinate ester). Moreover, MT was extremely light sensitive under the tested ICH conditions. The recommended storage condition for the ex-tempore prepared Triple IT solution is in a refrigerator (5 ± 3 °C) and protected from light. Primary packaging can be PhaSeal® syringes as well as glass vials. Under these conditions, no functionality-significant degradation is expected over a 24 hour storage period [2]. References: [1] A. Ruggiero, V. Conter, M. Milani, E. Biagi, I. Lazzareschi, P. Sparano, R. Riccardi. Intrathecal chemotherapy with antineoplastic agents in children. Paediatric drugs 3(4) (2001) 237-246. [2] M. D’Hondt, E. Vangheluwe, S. Van Dorpe, J. Boonen, T. Bauters, B. Pelfrene, J. Vandenbroucke, H. Robays, B. De Spiegeleer. Stability of ex-tempore prepared Triple intrathecal solution consisting of cytarabine, methotrexate and methylprednisolone sodium succinate. American Journal of Health-System Pharmacy, submitted for publication.
Please use this url to cite or link to this publication:
author
organization
year
type
conference
publication status
published
subject
keyword
methylprednisolone sodium succinate stability, cytarabine, methotrexate
in
Abstract book 15th forum of pharmaceutical sciences
conference name
15th Forum of Pharmaceutical Sciences
conference location
Spa, Belgium
conference start
2011-05-12
conference end
2011-05-13
language
English
UGent publication?
yes
classification
C3
copyright statement
I have retained and own the full copyright for this publication
id
1223790
handle
http://hdl.handle.net/1854/LU-1223790
date created
2011-05-14 12:28:57
date last changed
2016-12-19 15:35:09
@inproceedings{1223790,
  abstract     = {For the majority of children with acute lymphoblastic leukemia (ALL), treatment consists in part of a triple intrathecal (Triple IT) therapy, i.e. a combination of cytarabine (CB), methotrexate (MT) and methylprednisolone sodium succinate (MPSS) [1]. This combination product is prepared ex-tempore. However, no in-use shelf-life under defined storage conditions has yet been established. In this study, the short-term storage stability (up to 48 hours) was evaluated and included following study design variables: i) 3 packaging materials, i.e. PhaSeal{\textregistered} system, dark glass vial and dark glass vial + needles, ii) 4 storage conditions, i.e. light protected at 5 {\textdegree}C, 25 {\textdegree}C, 40 {\textdegree}C and photometric (UV and visible light) exposure at 25 {\textdegree}C, iii) batch reproducibility, i.e. 3 different batches. Calculation of the degradation kinetic parameters, obtained from HALO-HPLC-UV/DAD data, was performed using the Arrhenius equation to describe the temperature dependence. Moreover, identity of the major degradants was performed using ESI-MSn detection, and their specification relevance discussed. While CB is reasonably stable, MPSS did show hydrolysis as well as isomerisation (21- to 17-succinate ester). Moreover, MT was extremely light sensitive under the tested ICH conditions. The recommended storage condition for the ex-tempore prepared Triple IT solution is in a refrigerator (5 {\textpm} 3 {\textdegree}C) and protected from light. Primary packaging can be PhaSeal{\textregistered} syringes as well as glass vials. Under these conditions, no functionality-significant degradation is expected over a 24 hour storage period [2]. References:
[1]\unmatched{0009}A. Ruggiero, V. Conter, M. Milani, E. Biagi, I. Lazzareschi, P. Sparano, R. Riccardi. Intrathecal chemotherapy with antineoplastic agents in children. Paediatric drugs 3(4) (2001) 237-246.
[2]\unmatched{0009}M. D{\textquoteright}Hondt, E. Vangheluwe, S. Van Dorpe, J. Boonen, T. Bauters, B. Pelfrene, J. Vandenbroucke, H. Robays, B. De Spiegeleer. Stability of ex-tempore prepared Triple intrathecal solution consisting of cytarabine, methotrexate and methylprednisolone sodium succinate. American Journal of Health-System Pharmacy, submitted for publication.},
  author       = {D'Hondt, Matthias and Vangheluwe, Elien and Lemeire, Nadia and Bauters, Tieneke and PELFRENE, BRIGITTE and Vandenbroucke, Johan and Robays, Hugo and De Spiegeleer, Bart},
  booktitle    = {Abstract book 15th forum of pharmaceutical sciences},
  keyword      = {methylprednisolone sodium succinate stability,cytarabine,methotrexate},
  language     = {eng},
  location     = {Spa, Belgium},
  title        = {Short-term storage stability of Triple IT solution},
  year         = {2011},
}

Chicago
D’Hondt, Matthias, Elien Vangheluwe, Nadia Lemeire, TIENEKE BAUTERS, BRIGITTE PELFRENE, JOHAN VANDENBROUCKE, Hugo Robays, and Bart De Spiegeleer. 2011. “Short-term Storage Stability of Triple IT Solution.” In Abstract Book 15th Forum of Pharmaceutical Sciences.
APA
D’Hondt, Matthias, Vangheluwe, E., Lemeire, N., BAUTERS, T., PELFRENE, B., VANDENBROUCKE, J., Robays, H., et al. (2011). Short-term storage stability of Triple IT solution. Abstract book 15th forum of pharmaceutical sciences. Presented at the 15th Forum of Pharmaceutical Sciences.
Vancouver
1.
D’Hondt M, Vangheluwe E, Lemeire N, BAUTERS T, PELFRENE B, VANDENBROUCKE J, et al. Short-term storage stability of Triple IT solution. Abstract book 15th forum of pharmaceutical sciences. 2011.
MLA
D’Hondt, Matthias, Elien Vangheluwe, Nadia Lemeire, et al. “Short-term Storage Stability of Triple IT Solution.” Abstract Book 15th Forum of Pharmaceutical Sciences. 2011. Print.