Box-behnken design based statistical modelling for optimization of UPLC-MS/MS method for analysis of sorafenib in bulk and tablets

This study describes a Box-Behnken experimental design optimized procedure to develop ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for determination of sorafenib (SFB) in its bulk form and tablets. This approach enables optimization of chromatographic performance using fewer experiments and reduced cost of consumables. Neratinib, was used as an internal standard (IS) and the developed method was validated and it has been proved to be accurate, selective and rapid for the analysis. A reverse phase C18, UPLC, BEH™ column (50×2.1 mm, i.d. 1.7 μm, Waters, USA) was used for the analysis with a mobile phase composition of acetonitrile/water containing 0.15% formic acid 68/32 (v/v) and with isocratic flow at 0.31 mL/min. Multiple reaction monitoring ion transitions used for detection were m/z 465.31→252.05 and m/z 557.29→111.96 for SFB and IS, respectively. The linear range of the method was 3-500 ng/ml. The LOD and LOQ were found to be 1 ng/ml and 2.5 ng/ml, respectively. The method was successfully applied for analysis of SFB in bulk form and in tablets. The method was validated by linearity, precision, accuracy and showed no interference of additives used in the formulation. Copyright © 2015 American Scientific Publishers.