title: Quantification of 5,7-dimethoxyflavone in mouse plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and its application to a pharmacokinetic study.
abstract: 5,7-Dimethoxyflavone (5,7-DMF), a natural flavonoid abundant in many plants, has been reported to have many beneficial pharmacological effects, including strong chemopreventive and chemosensitizing properties, anti-oxidant, cardiovascular protectant, and anti-inflammatory activities. However, to date 5,7-DMF was evaluated mainly in vitro and its pharmacokinetics (PK) in vivo remains largely unknown. In addition, current available quantification methods of 5,7-DMF all lack sufficient sensitivity (lower limit of quantification >800 ng/mL). The purposes of our study are to establish a sensitive quantification method of 5,7-DMF using LC-MS/MS and evaluate the PK profile of 5,7-DMF in mouse. Our method was fully validated and all of the fundamental parameters in method validation, including accuracy, precision, sensitivity, selectivity, recovery and stability were evaluated thoroughly in mouse plasma. The calibration curve covered 2-1000 ng/mL with the lower limit of quantification (LLOQ) of 2 ng/mL. The inter-run and intra-run precision and accuracy were less than 15% of nominal concentrations. The matrix effect and recovery yield were within ±15% of nominal concentrations. In the PK study, 5,7-DMF was detectable in mouse plasma up to 21 h, with a terminal half-life of 11.5h. The clearance of 5,7-DMF (CL/F) is 22.3 L/h/kg and area under the curve (AUCinf) is 449 h ng/mL. In conclusion, a fast, accurate, sensitive and selective quantification method of 5,7-DMF was established and the developed method was successfully applied to a PK study of 5,7-DMF following oral administration of 5,7-DMF in mice.
authors.affiliation: Department of Pharmaceutics, University of Florida, Orlando, FL 32827, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Bei
authors.affiliation: Division of Pharmaceutics and Translational Therapeutics, University of Iowa, Iowa City, IA 52242, USA. Electronic address: guohua-an@uiowa.edu.
authors.forename: Guohua
authors.initials: G
authors.lastname: An
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005419:Flavonoids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D016014:Linear Models; D008297:Male; D051379:Mice; D064209:Phytochemicals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D005419:Flavonoids; D064209:Phytochemicals; C060298:5,7-dimethoxyflavone
keywords: 5,7-Dimethoxyflavone; LC–MS/MS; Natural product; Pharmacokinetics