Impurity profiling of mycophenolate mofetil with the assisstance of desirability function in method development
Abstract
Multicriteria decision making methodology in combination with experimental design has been applied for optimization of stability-indicating LC/DAD method of Mycophenolate mofetil and its degradation products. Via fractional factorial design variables with statistically significant impact on retention parameters of the investigated substances were defined and then thoroughly optimized toward four chromatographic responses combining central composition design and desirability function. The separation was achieved on Chromolith column (C18e, 100x4.6mm) with the mobile phase consisted of acetonitrile0.015M KH2PO4 (pH 4.4) (28:72, v/v). The flow rate of the mobile phase was 2mL/min and the detection was performed using PDA detector at 215nm. The method has been suitably modified for LC/MS/MS analysis. The ammonium-acetate buffer was used instead of phosphate buffer and pH of the water phase was adjusted with acetic acid. The flow rate was 1mLmin-1. The substance was subjected to stress cond...itions (0.01M NaOH, 1M HCl, 3-30% H2O2, 70 degrees C and day light). It resulted in formation of Mycophenolic acid and two oxidation products. The substance showed to be stable only towards photolysis. The LC/MS/MS values and fragmentation pattern of two unknown oxidation products were used in its characterization.
Keywords:
desirability function / experimental design / forced degradation studies / LC / MS / mycophenolate mofetilSource:
Journal of Liquid Chromatography & Related Technologies, 2011, 34, 12, 1014-1035Publisher:
- Taylor & Francis Inc, Philadelphia
Funding / projects:
- Synthesis, Quantitative Structure and Activity Relationship, Physico-Chemical Characterisation and Analysis of Pharmacologically Active Substances (RS-MESTD-Basic Research (BR or ON)-172033)
DOI: 10.1080/10826076.2011.569809
ISSN: 1082-6076
WoS: 000291807100006
Scopus: 2-s2.0-79959348395
Collections
Institution/Community
PharmacyTY - JOUR AU - Protić, Ana AU - Živanović, Ljiljana AU - Radisić, Marina AU - Lusevic, Mila PY - 2011 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1559 AB - Multicriteria decision making methodology in combination with experimental design has been applied for optimization of stability-indicating LC/DAD method of Mycophenolate mofetil and its degradation products. Via fractional factorial design variables with statistically significant impact on retention parameters of the investigated substances were defined and then thoroughly optimized toward four chromatographic responses combining central composition design and desirability function. The separation was achieved on Chromolith column (C18e, 100x4.6mm) with the mobile phase consisted of acetonitrile0.015M KH2PO4 (pH 4.4) (28:72, v/v). The flow rate of the mobile phase was 2mL/min and the detection was performed using PDA detector at 215nm. The method has been suitably modified for LC/MS/MS analysis. The ammonium-acetate buffer was used instead of phosphate buffer and pH of the water phase was adjusted with acetic acid. The flow rate was 1mLmin-1. The substance was subjected to stress conditions (0.01M NaOH, 1M HCl, 3-30% H2O2, 70 degrees C and day light). It resulted in formation of Mycophenolic acid and two oxidation products. The substance showed to be stable only towards photolysis. The LC/MS/MS values and fragmentation pattern of two unknown oxidation products were used in its characterization. PB - Taylor & Francis Inc, Philadelphia T2 - Journal of Liquid Chromatography & Related Technologies T1 - Impurity profiling of mycophenolate mofetil with the assisstance of desirability function in method development VL - 34 IS - 12 SP - 1014 EP - 1035 DO - 10.1080/10826076.2011.569809 ER -
@article{ author = "Protić, Ana and Živanović, Ljiljana and Radisić, Marina and Lusevic, Mila", year = "2011", abstract = "Multicriteria decision making methodology in combination with experimental design has been applied for optimization of stability-indicating LC/DAD method of Mycophenolate mofetil and its degradation products. Via fractional factorial design variables with statistically significant impact on retention parameters of the investigated substances were defined and then thoroughly optimized toward four chromatographic responses combining central composition design and desirability function. The separation was achieved on Chromolith column (C18e, 100x4.6mm) with the mobile phase consisted of acetonitrile0.015M KH2PO4 (pH 4.4) (28:72, v/v). The flow rate of the mobile phase was 2mL/min and the detection was performed using PDA detector at 215nm. The method has been suitably modified for LC/MS/MS analysis. The ammonium-acetate buffer was used instead of phosphate buffer and pH of the water phase was adjusted with acetic acid. The flow rate was 1mLmin-1. The substance was subjected to stress conditions (0.01M NaOH, 1M HCl, 3-30% H2O2, 70 degrees C and day light). It resulted in formation of Mycophenolic acid and two oxidation products. The substance showed to be stable only towards photolysis. The LC/MS/MS values and fragmentation pattern of two unknown oxidation products were used in its characterization.", publisher = "Taylor & Francis Inc, Philadelphia", journal = "Journal of Liquid Chromatography & Related Technologies", title = "Impurity profiling of mycophenolate mofetil with the assisstance of desirability function in method development", volume = "34", number = "12", pages = "1014-1035", doi = "10.1080/10826076.2011.569809" }
Protić, A., Živanović, L., Radisić, M.,& Lusevic, M.. (2011). Impurity profiling of mycophenolate mofetil with the assisstance of desirability function in method development. in Journal of Liquid Chromatography & Related Technologies Taylor & Francis Inc, Philadelphia., 34(12), 1014-1035. https://doi.org/10.1080/10826076.2011.569809
Protić A, Živanović L, Radisić M, Lusevic M. Impurity profiling of mycophenolate mofetil with the assisstance of desirability function in method development. in Journal of Liquid Chromatography & Related Technologies. 2011;34(12):1014-1035. doi:10.1080/10826076.2011.569809 .
Protić, Ana, Živanović, Ljiljana, Radisić, Marina, Lusevic, Mila, "Impurity profiling of mycophenolate mofetil with the assisstance of desirability function in method development" in Journal of Liquid Chromatography & Related Technologies, 34, no. 12 (2011):1014-1035, https://doi.org/10.1080/10826076.2011.569809 . .