title: Chiral analytical method development of liquiritigenin with application to a pharmacokinetic study.
abstract: Pharmacometric characterization studies of liquiritigenin have historically overlooked its chiral nature. To achieve complete characterization, an analytical method enabling the detection and quantification of the individual enantiomers of racemic (±) liquiritigenin is necessary. Resolution of the enantiomers of liquiritigenin was achieved using a simple high-performance liquid chromatographic method. A Chiralpak® ADRH column was employed to perform baseline separation with UV detection at 210 nm.The standard curves were linear ranging from 0.5 to 100 µg/mL for each enantiomer. Limit of quantification was 0.5 µg/mL. The assay was applied successfully to stereoselective serum disposition of liquiritigenin enantiomers in rats. Liquiritigenin enantiomers were detected in serum as both aglycones and glucuronidated conjugates. Both unconjugated enantiomers had a serum half-life of ~15 min in rats. The volume of distribution (V(d) ) for S- and R-liquiritigenin was 1.49 and 2.21 L/kg, respectively. Total clearance (Cl(total) ) was 5.12 L/h/kg for S-liquiritigenin and 4.79 L/h/kg for R-liquiritigenin, and area under the curve (AUC(0-inf) ) was 3.95 µg h/mL for S-liquiritigenin and 4.23 µg h/mL for R-liquiritigenin. The large volume of distribution coupled with the short serum half-life suggests extensive distribution of liquiritigenin into tissues.
authors: Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada, R3E 0T5.
authors: Casey L
authors: CL
authors: Sayre
authors: Mandi
authors: M
authors: Hopkins
authors: Jody K
authors: JK
authors: Takemoto
authors: Neal M
authors: NM
authors: Davies
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods; D044950:Flavanones / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
chemical_list: D044950:Flavanones; C083152:liquiritigenin