Analytical quality-by-design approach for sample treatment of BSA-containing solutions

摘要

The sample preparation of samples conlaining bovine serum albumin(BSA),e.g..as used in transdermal Franz diffusion cell(FDC) solutions,was evaluated using an analytical qualily-by-design(QbD)approach.Traditional precipitation of BSA by adding an equal volume of organic solvent,often successfully used with conventional HPLC-PDA,was found insufficiently robust when novel fused-core HPLC and/or UPLC-MS methods were used.In this study,three factors(acetonitrile(%).formic acid(%) and boiling time(min)) were included in the experimental design to determine an optimal and more suitable sample treatment of BSAcontaining FDC solutions.Using a QbD and Derringer desirability(D) approach,combining BSA loss,dilution factor and variability,we constructed an optimal working space with the edge of failure defined as D<0.9.The design space is modelled and is confirmed to have an ACN range of 83 ± 3% and FA content of 1 ±0.25%.