Analysis of Lidocaine Interactions with Serum Proteins Using High-Performance Affinity Chromatography

Authors

Sony Soman, University of Nebraska - Lincoln
Michelle J. Yoo, University of Nebraska - Lincoln
Yoon Jeong Jang, University of Nebraska - Lincoln
David S. Hage, University of Nebraska - LincolnFollow

Date of this Version

3-1-2010

Citation

Published in final edited form as: J Chromatogr B Analyt Technol Biomed Life Sci. 2010 March 1; 878(7-8): 705–708. doi:10.1016/j.jchromb. 2010.01.016. Version presented here is from NIH PubMed Central.

Comments

Copyright Elsevier Inc. Used by permission

Abstract

High-performance affinity chromatography was used to study binding by the drug lidocaine to human serum albumin (HSA) and α₁–acid glycoprotein (AGP). AGP had strong binding to lidocaine, with an association equilibrium constant (K_a) of 1.1-1.7 × 10⁵ M^-1 at 37 °C and pH 7.4. Lidocaine had weak-to-moderate binding to HSA, with a K_a in the range of 103 to 104 M^-1. Competitive experiments with site selective probes showed that lidocaine was interacting with Sudlow site II of HSA and the propranolol site of AGP. These results agree with previous observations in the literature and provide a better quantitative understanding of how lidocaine binds to these serum proteins and is transported in the circulation. This study also demonstrates how HPAC can be used to examine the binding of a drug with multiple serum proteins and provide detailed information on the interaction sites and equilibrium constants that are involved in such processes.