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

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

1,†
, 1,†
, 1
, 1
, 1
, 2
, 1
, 1
 and 1,*
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
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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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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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