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Stereospecific analytical method development and preliminary in vivo pharmacokinetic characterization of pinostrobin in the rat
Author(s) -
Sayre Casey L.,
Zhang Yangmiao,
Martinez Stephanie E.,
Takemoto Jody K.,
Davies Neal M.
Publication year - 2013
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.2834
Subject(s) - chemistry , enantiomer , chromatography , pharmacokinetics , calibration curve , resolution (logic) , detection limit , in vivo , stereochemistry , pharmacology , artificial intelligence , computer science , medicine , microbiology and biotechnology , biology
The complete pharmacokinetic disposition of the chiral flavonoid (±) pinostrobin remains unknown without the development of an analytical method of detection and quantitation of its individual enantiomers. Resolution of the enantiomers of pinostrobin was achieved using as simple high‐performance liquid chromatographic method. A Chiralpak® AD‐RH column was employed to perform baseline separation with UV detection at 287 nm. The standard curves were linear ranging from 0.5 to 100 µg/mL for each enantiomer. The limit of quantification was 0.5 µg/mL. Precision and accuracy of the assay was < 15% (RSD) and was with a bias <15% for all points on the calibration curve. The assay was applied successfully to stereoselective serum disposition of pinostrobin enantiomers in rats. Both enantiomers had a serum half‐life of ~7 h. They also shared similar values of volume of distribution ( V d S ‐pinostrobin, 8.2 L/kg; V d R ‐pinostrobin, 8.9 L/kg), total clearance ( S ‐pinostrobin CL total , 0.959 L//h/kg; R ‐pinostrobin CL total , 1.055 L//h/kg), and area under the curve ( S ‐pinostrobin AUC inf , 23.16 µg h/mL; R ‐pinostrobin AUC inf , 21.296 µg h/mL). The large volume of distribution suggests extensive distribution of pinostrobin into tissues. Copyright © 2012 John Wiley & Sons, Ltd.