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The bioanalytical challenge of determining unbound concentration and protein binding for drugs
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
2013 (English)In: Bioanalysis, ISSN 1757-6180, Vol. 5, no 24, 3033-3050 p.Article, review/survey (Refereed) Published
Abstract [en]

Knowledge regarding unbound concentrations is of vital importance when exploring the PK and PD of a drug. The accurate and reproducible determination of plasma protein binding and unbound concentrations for a compound/drug is a serious challenge for the bioanalytical laboratory. When the drug is in equilibrium with the binding protein(s), this equilibrium will shift when physiological conditions are not met. Furthermore, the true unbound fraction/concentration is unknown, and there are numerous publications in the scientific literature reporting and discussing data that have been produced without sufficient control of the parameters influencing the equilibrium. In this Review, different parameters affecting the equilibrium and analysis are discussed, together with suggestions on how to control these parameters in order to produce as trustworthy results for unbound concentrations/fractions as possible.

Place, publisher, year, edition, pages
2013. Vol. 5, no 24, 3033-3050 p.
National Category
Pharmaceutical Sciences Analytical Chemistry
Research subject
Analytical Pharmaceutical Chemistry
URN: urn:nbn:se:uu:diva-212927DOI: 10.4155/BIO.13.274ISI: 000330723000012OAI: oai:DiVA.org:uu-212927DiVA: diva2:679679
Available from: 2013-12-16 Created: 2013-12-16 Last updated: 2014-03-17Bibliographically approved

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