Stereospecific analytical method development and preliminary in vivo pharmacokinetic characterization of pinostrobin in the rat

Abstract

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.