Published Research - Department of Chemistry

 

Date of this Version

2013

Citation

Analyst (2013) 138, pp. 6262-6265; doi: 10.1039/c3an01315d

Comments

Copyright (c) 2013 The Royal Society of Chemistry. Used by permission.

Abstract

A multi-dimensional chromatographic approach was developed to measure the free fractions of drug enantiomers in samples that also contained a binding protein or serum. This method, which combined ultrafast affinity extraction with a chiral stationary phase, was demonstrated using the drug warfarin and the protein human serum albumin.

This report describes a multi-dimensional HPAC system that used ultrafast affinity extraction and chiral chromatography to simultaneously examine the free forms of drug enantiomers in complex samples (e.g., serum) and to study the binding of such drugs with proteins. R/S-Warfarin and its binding protein human serum albumin (HSA) were used as models to develop and evaluate this approach. Warfarin is an anticoagulant that is often used as a racemic mixture for the treatment of thromboembolic diseases, with the R- and S-enantiomers having noticeable differences in their pharmacokinetics and protein binding properties.3,10,11 HSA (molar mass, 66.5 kDa) is the main binding protein for warfarin and many other drugs in serum and is known to have strong interactions with both R- and S-warfarin at a region on this protein known as Sudlow site I.

Includes supplementary file.

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