期刊
JOURNAL OF CHROMATOGRAPHY A
卷 1217, 期 37, 页码 5761-5768出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.chroma.2010.07.023
关键词
Biomimetic chromatography; Human serum albumin stationary phase; Plasma protein binding; Lipophilicity; Charged species; Linear free energy relationships
资金
- Kapodistrias [E.L.K.E. 70/4/5876]
- University of Athens, Greece
- Hellenic State Scholarships Foundation
The retention behavior of 39 structurally diverse neutral, basic and acidic drugs was investigated on an HSA stationary phase using PBS buffer (pH 7.0) and acetonitrile or 2-propanol as organic modifiers. Extrapolated or directly measured log k(w) values as well as isocratic retention factors were correlated with plasma protein binding data taken from the literature. Retention factors determined in the presence of 10% acetonitrile led to high quality 1:1 correlation with apparent log K-HSA values. The derived reference equation was successfully validated using a secondary set of 24 drugs. Further analysis of HSA retention into more fundamental properties revealed the involvement of anionic species in solute-stationary phase interactions, expressed by the negatively charged fraction, besides the partitioning mechanism which was reflected by lipophilicity. Protonation of basic drugs, although less important, may also influence retention, leading to reduced partitioning into the HSA surface as a net effect, while it seems to have no effect on HSA binding. The above results were further confirmed by linear solvation energy relationships (LSER). (C) 2010 Elsevier B.V. All rights reserved.
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