High-throughput analysis of drug dissociation from serum proteins using affinity silica monoliths

Michelle J. Yoo, David S. Hage

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

A noncompetitive peak decay method was used with 1 mm× 4.6 mm id silica monoliths to measure the dissociation rate constants (k d) for various drugs with human serum albumin (HSA) and α 1-acid glycoprotein (AGP). Flow rates up to 9 mL/min were used in these experiments, resulting in analysis times of only 20-30 s. Using a silica monolith containing immobilized HSA, dissociation rate constants were measured for amitriptyline, carboplatin, cisplatin, chloramphenicol, nortriptyline, quinidine, and verapamil, giving values that ranged from 0.37 to 0.78 s -1. Similar work with an immobilized AGP silica monolith gave k d values for amitriptyline, nortriptyline, and lidocaine of 0.39-0.73 s -1. These k d values showed good agreement with values determined for drugs with similar structures and/or affinities for HSA or AGP. It was found that a k d of up to roughly 0.80 s -1 could be measured by this approach. This information made it possible to obtain a better understanding of the advantages and possible limitations of the noncompetitive peak decay method and in the use of affinity silica monoliths for the high-throughput analysis of drug-protein dissociation.

Original languageEnglish (US)
Pages (from-to)2255-2263
Number of pages9
JournalJournal of Separation Science
Volume34
Issue number16-17
DOIs
StatePublished - Aug 2011

Keywords

  • Affinity microcolumn
  • Drug-protein dissociation
  • HSA
  • Silica monolith
  • α -Acid glycoprotein

ASJC Scopus subject areas

  • Analytical Chemistry
  • Filtration and Separation

Fingerprint Dive into the research topics of 'High-throughput analysis of drug dissociation from serum proteins using affinity silica monoliths'. Together they form a unique fingerprint.

Cite this