Quantitative dynamic nuclear polarization-NMR on blood plasma for assays of drug meta

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Quantitative dynamic nuclear polarization-NMR on blood plasma for assays of drug metabolism.

Related Articles Quantitative dynamic nuclear polarization-NMR on blood plasma for assays of drug metabolism.

NMR Biomed. 2010 Sep 22;

Authors: Lerche MH, Meier S, Jensen PR, Hustvedt SO, Karlsson M, Duus JO, Ardenkjær-Larsen JH

Analytical platforms for the fast detection, identification and quantification of circulating drugs with a narrow therapeutic range are vital in clinical pharmacology. As a result of low drug concentrations, analytical tools need to provide high sensitivity and specificity. Dynamic nuclear polarization-NMR (DNP-NMR) in the form of the hyperpolarization-dissolution method should afford the sensitivity and spectral resolution for the direct detection and quantification of numerous isotopically labeled circulating drugs and their metabolites in single liquid-state NMR transients. This study explores the capability of quantitative in vitro DNP-NMR to assay drug metabolites in blood plasma. The lower limit of detection for the anti-epileptic drug (13)C-carbamazepine and its pharmacologically active metabolite (13)C-carbamazepine-10,11-epoxide is 0.08â??µg/mL in rabbit blood plasma analyzed by single-scan (13)C DNP-NMR. An internal standard is used for the accurate quantification of drug and metabolite. Comparison of quantitative DNP-NMR data with an established analytical method (liquid chromatography-mass spectrometry) yields a Pearson correlation coefficient r of 0.99. Notably, all DNP-NMR determinations were performed without analyte derivatization or sample purification other than plasma protein precipitation. Quantitative DNP-NMR is an emerging methodology which requires little sample preparation and yields quantitative data with high sensitivity for therapeutic drug monitoring. Copyright © 2010 John Wiley & Sons, Ltd.

PMID: 20862657 [PubMed - as supplied by publisher]



Source: PubMed