Show simple item record

dc.contributor.authorKamble, Sharad R.*
dc.contributor.authorLoadman, Paul M.*
dc.contributor.authorAbraham, M.H.*
dc.contributor.authorLiu, Xiangli*
dc.date.accessioned2017-11-20T17:00:06Z
dc.date.available2017-11-20T17:00:06Z
dc.date.issued2018-02
dc.identifier.citationKamble S, Loadman P, Abraham MH et al (2018) Structural properties governing drug-plasma protein binding determined by high-performance liquid chromatography method. Journal of Pharmaceutical and Biomedical Analysis. 149: 16-21.en_US
dc.identifier.urihttp://hdl.handle.net/10454/13844
dc.descriptionYesen_US
dc.description.abstractThe high-performance liquid chromatography (HPLC) method employing stationary phases immobilized with plasma proteins was used for this study to investigate the structural properties governing drug-plasma protein binding. A set of 65 compounds with a broad range of structural diversity (in terms of volume, hydrogen-bonding, polarity and electrostatic force) were selected for this purpose. The Abraham linear free energy relationship (LFER) analyses of the retention factors on the immobilized HSA (human serum albumin) and AGP (α1-acid glycoprotein) stationary phases showed that McGowan’s characteristic molecular volume (V), dipolarity/polarizability (S) and hydrogen bond basicity (B) are the three significant molecular descriptors of solutes determining the interaction with immobilized plasma proteins, whereas excess molar refraction (E) is less important and hydrogen bond acidity (A) is not of statistical significance in both systems, for electrically neutral compounds. It was shown that ionised acids, as carboxylate anions, bind very strongly to the immobilized HSA stationary phase and that ionised bases, as cations bind strongly to the AGP stationary phase. This is the first time that the effect of ionised species on plasma protein binding has been determined quantitatively; the increased binding of acids to HSA is due almost entirely to acids in their ionised form.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1016/j.jpba.2017.10.022en_US
dc.rights© 2017 Elsevier. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.en_US
dc.subjectPlasma proteins; Binding; HPLC; Retention factors (k); Linear free energy relationship; Abraham (Absolv) descriptorsen_US
dc.titleStructural properties governing drug-plasma protein binding determined by high-performance liquid chromatography methoden_US
dc.status.refereedYesen_US
dc.date.Accepted2017-10-22
dc.date.application2017-10-28
dc.typeArticleen_US
dc.type.versionAccepted Manuscripten_US
refterms.dateFOA2018-10-29T09:43:43Z


Item file(s)

Thumbnail
Name:
Liu_JPBA.pdf
Size:
517.5Kb
Format:
PDF
Description:
To keep suppressed
Thumbnail
Name:
Liu_et_al_JPBA.pdf
Size:
636.7Kb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record