Determination of the Pharmacokinetics and Oral Bioavailability of Salicylamine, a Potent [gamma]-Ketoaldehyde Scavenger, by LC/MS/MS

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...

Full description

Saved in:
Bibliographic Details
Published in:Pharmaceutics 2010-03, Vol.2 (1), p.18
Main Authors: Zagol-Ikapitte, Irene, Matafonova, Elena, Amarnath, Venkataraman, Bodine, Christopher L, Boutaud, Olivier, Tirona, Rommel G, Oates, John A, II, L Jackson Roberts, Davies, Sean S
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1999-4923
DOI:10.3390/pharmaceutics2010018