Equilibrium Dialysis, Ultracentrifugation, and Ultrafiltration in LC‐MS Bioanalysis

Chapter 3 Equilibrium Dialysis, Ultracentrifugation, and Ultrafiltration in LC-MS Bioanalysis Theo de Boer, Theo de BoerSearch for more papers by this authorHenri Meijering, Henri MeijeringSearch for more papers by this author Theo de Boer, Theo de BoerSearch for more papers by this authorHenri Meijering, Henri MeijeringSearch for more papers by this author Book Editor(s):Wenkui Li, Wenkui LiSearch for more papers by this authorWenying Jian, Wenying JianSearch for more papers by this authorYunlin Fu, Yunlin FuSearch for more papers by this author First published: 25 February 2019 https://doi.org/10.1002/9781119274315.ch3Citations: 1 AboutPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShareShare a linkShare onFacebookTwitterLinked InRedditWechat Summary In blood, a drug exists in two forms, bound and unbound. The specific drug's affinity to plasma proteins determines the proportion of the drug bound to plasma proteins, with the remainder being unbound. The unbound fraction is responsible for the pharmacologic effects. Therefore, characteristics such as membrane permeation, (metabolic) clearance and receptor binding are nowadays of major interest as the free or unbound fraction is likely to be a more accurate predictor of relationships between plasma levels and wanted/unwanted effects of the drugs of interest. Also, plasma protein binding and preferential partitioning of drugs into the erythrocytes are important factors in designing (early phase) clinical trials and hence need to be assessed early on in the drug development process. This chapter focusses on the three most widely used analytical techniques (equilibrium dialysis, ultrafiltration and ultracentrifugation) that are used for the determination of the unbound concentration and the plasma protein binding of drugs. Each technique is described in a separate section providing an overview of its specific advantages and disadvantages. Finally for each technique a generic experimental procedure is described. Citing Literature Sample Preparation in LC-MS Bioanalysis RelatedInformation