期刊
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
卷 879, 期 28, 页码 3041-3046出版社
ELSEVIER
DOI: 10.1016/j.jchromb.2011.08.043
关键词
9-Fluoropropyl-(+)-dihydrotetrabenazine; Pharmacokinetics; Liquid chromatography-tandem mass spectrometry; Microdialysis
资金
- National 973 Program [2011CB504105]
- National 863 Program [2006AA02A408]
To evaluate the penetration of the blood-brain barrier by 9-fluoropropyl-(+)-dihydrotetrabenazine (AV-133), microdialysis probes were implanted simultaneously into rat blood and brain, and a liquid chromatography-tandem mass spectrometric method was developed and validated to monitor the AV-133 concentration in the microdialysates. The chromatographic separation was performed on an XTerra C-18 column (150 mm x 2.1 mm id., 5 mu m particles) with gradient elution. The mass spectrometer was operated in positive mode using electrospray ionization. The analytes were measured using the multiple-reaction-monitoring mode. The calibration curves were linear over the range of 5.00-1000 ng/mLAV-133, with a coefficient of determination >0.995. The accuracies ranged from 99.5% to 105.0% and the precisions were <10% for AV-133. This method was used to determine the concentrations of AV-133 and its pharrnacokinetics in the brains and blood of rats. The blood and brain concentration-time profiles for AV-133 were obtained, and the blood-brain barrier penetration was evaluated. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.
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