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

✍ Scribed by Michelle J. Yoo; David S. Hage

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 288 KB
• Volume: 34
• Category: Article
• ISSN: 1615-9306
• DOI: 10.1002/jssc.201100280

✦ Synopsis

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.