Review Article
An Extraction Assay Analysis for Galanthamine in Guinea Pig Plasma and its Application to Nerve Agent Countermeasures
Wes E Steiner1*, Ioannis A Pikalov1, Patrick T Williams2, William A English2 and Corey J Hilmas3
1Department of Chemistry and Biochemistry, Eastern Washington University, USA
2Neurobehavioral Toxicology Branch, Analytical Toxicology Division, U.S. Army Medical Research Institute of Chemical Defense, USA
3Division of Dietary Supplement Programs, Office of Nutrition, Labeling, and Dietary Supplements, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, USA
- *Corresponding Author:
- Wes E Steiner
Department of Chemistry and Biochemistry
Eastern Washington University, 226 Science Building
Cheney, WA 99004, USA
Tel: (509)359-6521
Fax: (509)359-6973
E-mail: wsteiner@ewu.edu
Received date: July 18, 2012; Accepted date: August 21, 2012; Published date: August 28, 2012
Citation: Steiner WE, Pikalov IA, Williams PT, English WA, Hilmas CJ (2012) An Extraction Assay Analysis for Galanthamine in Guinea Pig Plasma and its Application to Nerve Agent Countermeasures. J Anal Bioanal Tech 3:144. doi: 10.4172/2155-9872.1000144
Copyright: © 2012 Steiner WE, 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
Galanthamine hydrobromide (GAL HBr), approved material for treatment of mild to moderate Alzheimer’s disease, is a centrally-acting reversible acetylcholinesterase inhibitor (AChEI) that is currently under evaluation as a therapeutic countermeasure against organophosphorus G- and V-Series nerve agents, which can induce rapid lethality in guinea pigs and humans. It has been shown that upon combination with atropine (ATR) and pyridine-2-aldoxime methochloride (2-PAM), a single dose of GAL administered before or soon after the acute exposure to a lethal dose of organophosphorus compounds can safely counteract toxicity in guinea pigs. To that end a new sample preparation extraction method analysis assay has been explored to enable future high-throughput, reproducible, and sensitive assays for the extraction of galanthamine in guinea pig plasma. Samples were prepared with diphenhydramine hydrochloride (DPH HCl) internal standard and recovered with 10 min liquid-liquid trichloromethane extractions. Samples were analyzed with a reversed phase liquid chromatographic column interfaced to a triple quadrupole mass spectrometer (LC/MS/MS) operating in the positive ion multiple reaction monitoring (MRM) Turbo Ionspray mode. Precursor to product ion (M+H)+ transitions of 288-to-213 m/z and 256-to-167 m/z for GAL and DPH were observed, respectively. Sample run times of 1.50 min were achieved.