Analytical Methods for the Bioavailability Evaluation of Hydroxypyridinonate Actinide Decorporation Agents in Pre-Clinical Pharmacokinetic Studies
- *Corresponding Author:
- Rebecca J. Abergel
Chemical Sciences Division, Lawrence Berkeley National Laboratory
Berkeley, California, USA
E-mail: [email protected]
Received Date: November 22, 2011; Accepted Date: December 09, 2011; Published Date: December 11, 2011
Citation: Chang PY, Bunin DI, Gow J, Swezey R, Shinn W, et al. (2011) Analytical Methods for the Bioavailability Evaluation of Hydroxypyridinonate Actinide Decorporation Agents in Pre-Clinical Pharmacokinetic Studies. J Chromatograph Separat Techniq 4:196 doi:10.4172/2157-7064.1000196
Copyright: © 2011 Chang PY, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The hydroxypyridinonate ligands 5-LIO(Me-3,2-HOPO) and 3,4,3-LI(1,2-HOPO) are two lead compounds under development for actinide chelation therapy. Methods to quantify these actinide decorporation agents in plasma are necessary to study their in vivo pharmacokinetic behavior. Such bioanalytical methods were developed with rat plasma, using liquid chromatography coupled with tandem mass spectrometry, and have a detection range of 0.05 to 2.5 μg/mL and 0.1 to 5 μg/mL for 5-LIO(Me-3,2-HOPO) and 3,4,3-LI(1,2-HOPO), respectively. These methods were used to determine the in vivo plasma pharmacokinetics of the free acid and four salt forms of each ligand after a single intravenous or oral administration in rats. The different salt forms displayed similar pharmacokinetic profiles to those of the corresponding free acid, and the use of salt co-formers did not improve the oral bioavailability of the active pharmaceutical ingredients in rats. The described bioanalytical detection methods were successfully applied to the selection of solid-state forms of 5Ã¢ÂÂLIO(Me-3,2-HOPO) and 3,4,3-LI(1,2-HOPO) for future preclinical development activities, and will be adapted for use with plasma from other species.