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Determination of brain and plasma drug concentrations by liquid chromatography/tandem mass spectrometry
Author(s) -
Tamvakopoulos C. S.,
Colwell L. F.,
Barakat K.,
FenykMelody J.,
Griffin P. R.,
Nargund R.,
Palucki B.,
Sebhat I.,
Shen X.,
Stearns R. A.
Publication year - 2000
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/1097-0231(20001015)14:19<1729::aid-rcm85>3.0.co;2-5
Subject(s) - chemistry , chromatography , dosing , analyte , tandem mass spectrometry , liquid chromatography–mass spectrometry , mass spectrometry , solid phase extraction , drug , penetration (warfare) , pharmacology , organic chemistry , medicine , operations research , engineering
A method is described for the evaluation of drug concentrations in plasma and brain from treated rats. The analyte is recovered from plasma or brain homogenate by liquid‐liquid extraction and subsequently analyzed by liquid chromatography/tandem mass spectrometry (LC/MS/MS). A simple experimental protocol renders the procedure valuable for obtaining information rapidly on brain penetration and plasma exposure of specific classes of compounds. This methodology has been applied to evaluate brain penetration with 30 different compounds from the same discovery program. In an attempt to increase throughput in our screening efforts, mixture dosing was evaluated. Results from single compound administration were compared with results following administration of a mixture of four compounds. Preliminary results, with specific classes of compounds, show no major differences (ranking order) in brain or plasma concentrations between mixture dosing and single compound administration, suggesting that mixture dosing could be applicable to brain penetration studies in the drug discovery phase. Copyright © 2000 John Wiley & Sons, Ltd.