alexa Analytical Methods for the Bioavailability Evaluation of Hydroxypyridinonate Actinide Decorporation Agents in Pre-Clinical Pharmacokinetic Studies | OMICS International | Abstract
ISSN: 2157-7064

Journal of Chromatography & Separation Techniques
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Research Article

Analytical Methods for the Bioavailability Evaluation of Hydroxypyridinonate Actinide Decorporation Agents in Pre-Clinical Pharmacokinetic Studies

Polly Y. Chang1, Deborah I. Bunin1, Jason Gow1, Robert Swezey1, Walter Shinn1, David K. Shuh2 and Rebecca J. Abergel2*

1Biosciences Division, SRI International, Menlo Park, CA 94025, USA

2Chemical Sciences Division, The Glenn T. Seaborg Center, Lawrence Berkeley National Laboratory, Berkeley CA 94720, USA

*Corresponding Author:
Rebecca J. Abergel
Chemical Sciences Division, Lawrence Berkeley National Laboratory
Berkeley, California, USA
Tel: 510-486-5249
Fax: 510-486-5587
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.

Abstract

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 5‑LIO(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.

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