Determination of the pharmacokinetics and oral bioavailability of salicylamine, a potent γ-ketoaldehyde scavenger, by LC/MS/MS

Authors

Irene Zagol-Ikapitte, Vanderbilt University
Elena Matafonova, Vanderbilt University
Venkataraman Amarnath, Vanderbilt University
Christopher L. Bodine, Vanderbilt University
Olivier Boutaud, Vanderbilt University
Rommel G. Tirona, Schulich School of Medicine & DentistryFollow
John A. Oates, Vanderbilt University
L. Jackson Roberts, Vanderbilt University
Sean S. Davies, Vanderbilt University

Document Type

Article

Publication Date

3-1-2010

Journal

Pharmaceutics

Volume

2

Issue

1

First Page

18

Last Page

29

URL with Digital Object Identifier

10.3390/pharmaceutics2010018

Abstract

Levels of reactive γ-ketoaldehydes derived from arachidonate increase in diseases associated with inflammation and oxidative injury. To assess the biological importance of these γ-ketoaldehydes, we previously identified salicylamine as an effective γ-ketoaldehyde scavenger in vitro and in cells. To determine if salicylamine could be administered in vivo, we developed an LC/MS/MS assay to measure salicylamine in plasma and tissues. In mice, half-life (t1/2) was 62 minutes. Drinking water supplementation (1-10 g/L) generated tissue concentrations (10-500 μM) within the range previously shown to inhibit γ-ketoaldehydes in cells. Therefore, oral administration of salicylamine can be used to assess the contribution of γ-ketoaldehydes in animal models of disease. © 2010 by the authors licensee Molecular Diversity Preservation International, Basel, Switzerland.