Quantitative dynamic nuclear polarization-NMR on blood plasma for assays of drug metabolism.
NMR Biomed
; 24(1): 96-103, 2011 Jan.
Article
em En
| MEDLINE
| ID: mdl-20862657
ABSTRACT
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 0.08 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasma
/
Bioensaio
/
Carbamazepina
/
Espectroscopia de Ressonância Magnética
Limite:
Animals
Idioma:
En
Revista:
NMR Biomed
Assunto da revista:
DIAGNOSTICO POR IMAGEM
/
MEDICINA NUCLEAR
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Dinamarca