Impurity profiling of mycophenolate mofetil with the assisstance of desirability function in method development
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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 mofetil
Source:Journal of Liquid Chromatography & Related Technologies, 2011, 34, 12, 1014-1035
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