Characterization of drug interactions with soluble β-cyclodextrin by high-performance affinity chromatography

Jianzhong Chen, Corey M. Ohnmacht, David S. Hage

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

This study examined the use of an immobilized human serum albumin (HSA) column to study solution-phase reactions between drugs and β-cyclodextrin (β-CD). Chromatographic equations were developed to characterize the binding of chemicals to a soluble ligand (β-CD) in the presence of an independent immobilized ligand (HSA). Situations considered included the presence of both a homogeneous and heterogeneous immobilized ligand, as well as complex interactions between the chemical of interest and soluble ligand. Three drugs (warfarin, tamoxifen, and phenytoin) were examined by this approach. This method involved injecting a small amount of each drug onto an HSA column in the presence of various concentrations of β-CD in the mobile phase. By measuring the change in the drug's retention factor as the concentration of β-CD was varied, it was possible to determine the stability constant between the injected drug and β-CD. With this approach, warfarin and β-CD were found to have 1:1 interactions with a stability constant of 5.2×102M-1 at 37°C and pH 7.4, a result in close agreement with previous literature values. Tamoxifen and phenytoin were also found to have 1:1 interactions with β-CD and had stability constants of 0.9-1.2×104 and 6-9×102M-1, respectively. With these latter solutes, the effects of secondary binding to the chromatographic support had to be considered. The theory and methods described in this report are not limited to these drugs and β-CD but can be applied to other analytes and soluble ligands.

Original languageEnglish (US)
Pages (from-to)115-126
Number of pages12
JournalJournal of Chromatography A
Volume1033
Issue number1
DOIs
StatePublished - Apr 9 2004

Fingerprint

Drug interactions
Affinity chromatography
Cyclodextrins
Drug Interactions
Affinity Chromatography
Ligands
Serum Albumin
Pharmaceutical Preparations
Phenytoin
Warfarin
Tamoxifen

Keywords

  • Affinity sorbents
  • Pharmaceutical analysis
  • Phenytoin
  • Stability constants
  • Tamoxifen
  • Warfarin

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Organic Chemistry

Cite this

Characterization of drug interactions with soluble β-cyclodextrin by high-performance affinity chromatography. / Chen, Jianzhong; Ohnmacht, Corey M.; Hage, David S.

In: Journal of Chromatography A, Vol. 1033, No. 1, 09.04.2004, p. 115-126.

Research output: Contribution to journalArticle

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