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 language | English (US) |
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Pages (from-to) | 2255-2263 |
Number of pages | 9 |
Journal | Journal of Separation Science |
Volume | 34 |
Issue number | 16-17 |
DOIs | |
State | Published - Aug 2011 |
Keywords
- Affinity microcolumn
- Drug-protein dissociation
- HSA
- Silica monolith
- α -Acid glycoprotein
ASJC Scopus subject areas
- Analytical Chemistry
- Filtration and Separation