Journal
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
Volume 878, Issue 30, Pages 3193-3197Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jchromb.2010.09.033
Keywords
Human serum albumin; High-performance affinity chromatography; Glycation; Drug-protein binding; Sulfonylurea drugs; Fatty acids
Funding
- National Institutes of Health [R01 DK069629, RR015468]
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This report examines the use of high-performance affinity chromatography as a screening tool for studying the change in binding by sulfonylurea drugs to the protein human serum albumin (HSA) during diabetes. The effects of both the non-enzymatic glycation of HSA and the presence of fatty acids on these interactions were considered using a zonal elution format. It was found that there was a significant increase (i.e., 2.7- to 3.6-fold) in the relative retention of several sulfonylurea drugs (i.e., acetohexamide, tolbutamide, glybenclamide and gliclazide) on columns containing normal versus glycated HSA. The addition of various long chain fatty acids to the mobile phase gave the same trend in retention for the tested drugs on both the HSA and glycated HSA columns, generally leading to lower binding. Most of the fatty acids examined produced similar or moderately different relative shifts in retention; however, palmitic acid was found to produce a much larger change in retention on columns containing glycated HSA versus normal HSA under the conditions used in this study. (C) 2010 Elsevier B.V. All rights reserved.
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