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

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237312PMC
http://dx.doi.org/10.1002/bmc.2787DOI Listing

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