title: Quantitative determination of myricetin in rat plasma by ultra performance liquid chromatography tandem mass spectrometry and its absolute bioavailability.
abstract: Myricetin is a widely distributed bioactive flavonoid with scientific interest attributed to its anti-oxidant, antitumor, and anti-inflammatory properties. A specific and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated for identification and quantification of myricetin in rat plasma after oral and intravenous administrations. Kaempferol was used as an internal standard. Followed by β-glucuronidase and sulfatase hydrolysis and liquid-liquid extraction with ethyl acetate, the analytes were separated on an Acquity UPLC BEH C18 column (2.1×50 mm, 1.7 μm) and analyzed in the selected ion recording with a negative electrospray ionization mode. The developed method was validated for selectivity, accuracy, precision, linearity, recovery, stability and matrix effect. The assay was validated over a wide concentration range of 2-4,000 ng/mL. Intra- and inter-day precisions were all less than 13.49% and accuracy ranged from 95.75 to 109.80%. The present method was successfully applied to investigate a pharmacokinetic study of myricetin following intravenous and oral administrations to rats. The absolute bioavailability was found to be 9.62% and 9.74% at 2 oral doses (50 mg/kg and 100 mg/kg, respectively), which indicated myricetin was poorly absorbed after oral administration. To our knowledge, this is the first pharmacokinetic evaluation of myricetin as a single active pharmaceutical ingredient in preclinical studies.
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Dang
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: G
authors.initials: G
authors.lastname: Lin
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Duan
authors.affiliation: Global Pharmaceutical Research and Development, Hospira Inc., McPherson, KS, USA.
authors.forename: P
authors.initials: P
authors.lastname: Ma
authors.affiliation: Pharmacy Department, Shanghai TCM-integrated Hospital, Shanghai, China.
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: G
authors.initials: G
authors.lastname: Ji
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002138:Calibration; D002853:Chromatography, Liquid / Q000592:standards; D005419:Flavonoids / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D005419:Flavonoids; C040015:myricetin