Chiral analytical method development of liquiritigenin with application to a pharmacokinetic study

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. Copyright © 2012 John Wiley & Sons, Ltd.