Studies of drug interactions with alpha1-acid glycoprotein by using on-line immunoextraction and high-performance affinity chromatography

Cong Bi, Ryan Matsuda, Chenhua Zhang, Zitha Isingizwe, William Clarke, David S. Hage

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

A method that combined on-line immunoextraction with high-performance affinity chromatography was developed to examine the binding of drugs with α1-acid glycoprotein (AGP). Affinity microcolumns containing immobilized polyclonal anti-AGP antibodies were developed that had a capture efficiency of up to 98.4% for AGP and a binding capacity of 0.72 nmol AGP when using a 20 mm × 2.1 mm i.d. microcolumn. These microcolumns were employed in various formats to examine the binding of drugs to normal AGP and AGP that had been adsorbed from serum samples for patients with systemic lupus erythematosus (SLE). Drugs that were screened in zonal elution experiments for their overall binding to these types of AGP included chlorpromazine, disopyramide, imipramine, propranolol, and warfarin. Most of these drugs showed an increase in their binding to the AGP from SLE serum when compared to normal AGP (i.e., an increase of 13–76%); however, disopyramide gave a 21–25% decrease in retention when the same AGP samples were compared. Frontal analysis was used to further evaluate the binding of disopyramide and imipramine to these forms of AGP. Both drugs gave a good fit to a model that involved a combination of saturable and non-saturable interactions with AGP. Changes in the non-saturable interactions accounted for most of variations seen in the binding of disopyramide and imipramine with the AGP samples. The methods used in this study could be adapted for use in personalized medicine and the study of other proteins or drugs using aqueous mixtures or clinical samples.

Original languageEnglish (US)
Pages (from-to)64-73
Number of pages10
JournalJournal of Chromatography A
Volume1519
DOIs
StatePublished - Oct 13 2017

Keywords

  • Alpha-acid glycoprotein
  • Drug-protein interactions
  • High-performance affinity chromatography
  • Immunoextraction
  • Personalized medicine
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Studies of drug interactions with alpha<sub>1</sub>-acid glycoprotein by using on-line immunoextraction and high-performance affinity chromatography'. Together they form a unique fingerprint.

  • Cite this