title: Determination of pharmacokinetics of chrysin and its conjugates in wild-type FVB and Bcrp1 knockout mice using a validated LC-MS/MS method.
abstract: Chrysin, a flavone found in many plants, is also available as a dietary supplement because of its reported anticancer activities. However, its bioavailability is very poor due to extensive phase II metabolism. The purpose of this study was to develop an UPLC-MS/MS method to simultaneously quantify chrysin and its phase II metabolites, and to determine its pharmacokinetics in FVB wild-type and Bcrp knockout (Bcrp1 -/-) mice. In addition, the role of BCRP in chrysin phase II disposition was further investigated in Caco-2 cells. The results showed that our sensitive and reproducible UPLC-MS/MS method was successfully applied to the pharmacokinetic study of chrysin in wild-type and Bcrp1 (-/-) FVB mice after oral administration (20 mg/kg). Although there was no significant change in systemic exposure of chrysin and its metabolites, it was found that the Tmax for chrysin glucuronide was significantly shorter (p < 0.01) in Bcrp1-deficient mice. Furthermore, it was shown that inhibition of BCRP by Ko143 significantly reduced the efflux of chrysin sulfate in Caco-2 cells. In conclusion, BCRP had significant but less than expected impact on pharmacokinetics of chrysin and its conjugates, which were determined using a newly developed and validated LC-MS/MS method.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, Texas 77030, United States.
authors.forename: Shufan
authors.initials: S
authors.lastname: Ge
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, Texas 77030, United States.
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, Texas 77030, United States.
authors.forename: Taijun
authors.initials: T
authors.lastname: Yin
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, Texas 77030, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000172:deficiency / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005419:Flavonoids / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; D000970:Antineoplastic Agents; D005419:Flavonoids; C043561:chrysin
keywords: BCRP; UPLC-MS/MS; chrysin; conjugates; pharmacokinetics