Journal article
Quantification of 5,7-dimethoxyflavone in mouse plasma using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and its application to a pharmacokinetic study
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, Vol.978-979, pp.11-17
01/26/2015
DOI: 10.1016/j.jchromb.2014.11.018
PMID: 25531865
Abstract
•Highly sensitive LC–MS/MS method of 5,7-DMF in mouse plasma was established.•Full validations, accuracy and precision parameters all passed the FDA criteria.•Matrix effect and recovery yield were consistent within linear range.•Plasma samples were stable for 2 weeks and up to three freeze–thaw cycles.•The first report on 5,7-dimethoxyflavone pharmacokinetics in mice.
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 >800ng/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 2–1000ng/mL with the lower limit of quantification (LLOQ) of 2ng/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 21h, with a terminal half-life of 11.5h. The clearance of 5,7-DMF (CL/F) is 22.3L/h/kg and area under the curve (AUCinf) is 449hng/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.
Details
- Title: Subtitle
- Quantification of 5,7-dimethoxyflavone in mouse plasma using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and its application to a pharmacokinetic study
- Creators
- Di Bei - Department of Pharmaceutics, University of Florida, Orlando, FL 32827, USAGuohua An - Division of Pharmaceutics and Translational Therapeutics, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, Vol.978-979, pp.11-17
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.jchromb.2014.11.018
- PMID
- 25531865
- ISSN
- 1570-0232
- eISSN
- 1873-376X
- Grant note
- DOI: 10.13039/100006804, name: University of Florida
- Language
- English
- Date published
- 01/26/2015
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984065311502771
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