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Determination of the Pharmacokinetics and Oral Bioavailability of Salicylamine, a Potent γ-Ketoaldehyde Scavenger, by LC/MS/MS
Division of Clinical Pharmacology, Departments of Pharmacology, Medicine, and Pathology, Vanderbilt University, Nashville, TN, USA
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; in revised form: 13 January 2010 / Accepted: 28 January 2010 / Published: 1 February 2010
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
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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.
Zagol-Ikapitte I, Matafonova E, Amarnath V, Bodine CL, Boutaud O, Tirona RG, Oates JA, Roberts II LJ, Davies SS. Determination of the Pharmacokinetics and Oral Bioavailability of Salicylamine, a Potent γ-Ketoaldehyde Scavenger, by LC/MS/MS. Pharmaceutics. 2010; 2(1):18-29.
Zagol-Ikapitte, Irene; Matafonova, Elena; Amarnath, Venkataraman; Bodine, Christopher L.; Boutaud, Olivier; Tirona, Rommel G.; Oates, John A.; Roberts II, L. Jackson; Davies, Sean S. 2010. "Determination of the Pharmacokinetics and Oral Bioavailability of Salicylamine, a Potent γ-Ketoaldehyde Scavenger, by LC/MS/MS." Pharmaceutics 2, no. 1: 18-29.