title: Chiral analytical method development and application to pre-clinical pharmacokinetics of pinocembrin.
abstract: An analytical method enabling the detection and quantification of the individual enantiomers of racemic (±) pinocembrin is required to fully characterize its pharmacokinetic disposition. Direct resolution of the enantiomers of pinocembrin was achieved using a novel and simple reversed-phase high-performance liquid chromatography method with electrospray ionization and detection by mass spectrometry in rat serum. A Chiralcel® AD-RH column was employed to perform baseline separation with electrospray positive-mode ionization with selected ion monitoring detection. The standard curves were linear from 0.5 to 100 µg/mL for each enantiomer. The limit of quantification was 0.5 µg/mL. The assay was applied successfully to stereoselective serum disposition of pinocembrin enantiomers in rats. Pinocembrin enantiomers were detected in serum. Both enantiomers had a serum half-life of ~15 min in rats. Similar values of volume of distribution between the enantiomers were also observed: 1.76 L/kg for S-pinocembrin and 1.79 L/kg for R-pinocembrin. Total clearance was 5.527 L//h/kg for S-pinocembrin and 5.535 L/h/kg for R-pinocembrin, and the area under the curve was 1.821 µg h/mL for S-pinocembrin and 1.876 µg h/mL for R-pinocembrin. The large volume of distribution coupled with the short serum half-life suggests extensive distribution of pinocembrin into the tissues.
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada, R3E 0T5.
authors.forename: Casey L
authors.initials: CL
authors.lastname: Sayre
authors.forename: Jody K
authors.initials: JK
authors.lastname: Takemoto
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Martinez
authors.forename: Neal M
authors.initials: NM
authors.lastname: Davies
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D056148:Chromatography, Reverse-Phase / Q000379:methods; D003374:Coumarins / Q000737:chemistry; D044950:Flavanones / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D016018:Least-Squares Analysis; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013237:Stereoisomerism
chemical_list: D003374:Coumarins; D044950:Flavanones; C017299:7-ethoxycoumarin; C016063:pinocembrin