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Pharmaceutics 2010, 2(1), 18-29; doi:10.3390/pharmaceutics2010018

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

1
Division of Clinical Pharmacology, Departments of Pharmacology, Medicine, and Pathology, Vanderbilt University, Nashville, TN, USA
2
Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 16 December 2009 / Revised: 13 January 2010 / Accepted: 28 January 2010 / Published: 1 February 2010
(This article belongs to the Special Issue Applications of Hyphenated Chromatography Techniques in Pharmaceutics)
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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.
Keywords: levuglandins; isoketals; aldehydes; scavengers; oxidative stress; inflammation; lipid peroxidation; bioavailability; pharmacokinetics levuglandins; isoketals; aldehydes; scavengers; oxidative stress; inflammation; lipid peroxidation; bioavailability; pharmacokinetics
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Zagol-Ikapitte, I.; Matafonova, E.; Amarnath, V.; Bodine, C.L.; Boutaud, O.; Tirona, R.G.; Oates, J.A.; Roberts II, L.J.; Davies, S.S. Determination of the Pharmacokinetics and Oral Bioavailability of Salicylamine, a Potent γ-Ketoaldehyde Scavenger, by LC/MS/MS. Pharmaceutics 2010, 2, 18-29.

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