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...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%.展开更多
基金the Special Research Fund of Ghent University(BOF 01D23812 to Lien Taevernier and BOF O1J22510 to Evelien Wynendaele and Professor Bart De Spiegeleer)the Institute for the Promotion of Innovation through Science and Technology in Flanders(IWT 101529 to Matthias D'Hondt)for their financial funding
文摘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%.
