Kinetic studies of drug-protein interactions by using peak profiling and high-performance affinity chromatography

Examination of multi-site interactions of drugs with human serum albumin columns

Zenghan Tong, John E. Schiel, Efthimia Papastavros, Corey M. Ohnmacht, Quentin R. Smith, David S Hage

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Carbamazepine and imipramine are drugs that have significant binding to human serum albumin (HSA), the most abundant serum protein in blood and a common transport protein for many drugs in the body. Information on the kinetics of these drug interactions with HSA would be valuable in understanding the pharmacokinetic behavior of these drugs and could provide data that might lead to the creation of improved assays for these analytes in biological samples. In this report, an approach based on peak profiling was used with high-performance affinity chromatography to measure the dissociation rate constants for carbamazepine and imipramine with HSA. This approach compared the elution profiles for each drug and a non-retained species on an HSA column and control column over a board range of flow rates. Various approaches for the corrections of non-specific binding between these drugs and the support were considered and compared in this process. Dissociation rate constants of 1.7 (±0.2)s -1 and 0.67 (±0.04)s -1 at pH 7.4 and 37°C were estimated by this approach for HSA in its interactions with carbamazepine and imipramine, respectively. These results gave good agreement with rate constants that have determined by other methods or for similar solute interactions with HSA. The approach described in this report for kinetic studies is not limited to these particular drugs or HSA but can also be extended to other drugs and proteins.

Original languageEnglish (US)
Pages (from-to)2065-2071
Number of pages7
JournalJournal of Chromatography A
Volume1218
Issue number15
DOIs
StatePublished - Apr 15 2011

Fingerprint

Affinity chromatography
Drug Interactions
Affinity Chromatography
Serum Albumin
Kinetics
Imipramine
Pharmaceutical Preparations
Carbamazepine
Proteins
Rate constants
Drug interactions
Pharmacokinetics
Blood Proteins
Assays
Carrier Proteins
Blood
Flow rate

Keywords

  • Carbamazepine
  • Drug-protein binding
  • High-performance affinity chromatography
  • Human serum albumin
  • Imipramine
  • Peak profiling

ASJC Scopus subject areas

  • Analytical Chemistry
  • Organic Chemistry
  • Biochemistry

Cite this

Kinetic studies of drug-protein interactions by using peak profiling and high-performance affinity chromatography : Examination of multi-site interactions of drugs with human serum albumin columns. / Tong, Zenghan; Schiel, John E.; Papastavros, Efthimia; Ohnmacht, Corey M.; Smith, Quentin R.; Hage, David S.

In: Journal of Chromatography A, Vol. 1218, No. 15, 15.04.2011, p. 2065-2071.

Research output: Contribution to journalArticle

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