title: A sensitive LC-MS/MS method for simultaneous determination of six flavonoids in rat plasma: application to a pharmacokinetic study of total flavonoids from mulberry leaves.
abstract: A simple and sensitive LC-MS/MS method has been developed and validated for the determination of rutin, isoquercitrin, astragalin, quercetin, kaempferol and isorhamnetin in rat plasma using naringin as the internal standard (IS). The plasma samples were pretreated and extracted by liquid-liquid extraction. Chromatographic separation was accomplished on a C18 column with a 10 min gradient elution using acetonitrile and 0.1% formic acid aqueous solution as mobile phase at a flow rate of 0.3 mL min(-1). A tandem mass spectrometric detection was conducted using multiple reaction monitoring (MRM) via an electrospray ionization (ESI) source and operating in the negative ionization mode. The lower limit of quantitation (LLOQ) of each analyte was lower than 1 ng mL(-1). Intra-day and inter-day precisions were less than 11.9%. The relative errors of accuracy were in the range of -9.2% to 6.1%. The mean recoveries of flavonoids and IS were higher than 53.8%. The proposed method was further applied to investigate the pharmacokinetics of all analytes after a single oral administration of total flavonoids from mulberry leaves to rats.
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.forename: Hui-Zi
authors.initials: HZ
authors.lastname: Ouyang
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.forename: Yan-Xu
authors.initials: YX
authors.lastname: Chang
authors.forename: Gui-Xiang
authors.initials: GX
authors.lastname: Pan
authors.forename: Gai-Ying
authors.initials: GY
authors.lastname: Dong
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Xiu-Mei
authors.initials: XM
authors.lastname: Gao
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D005419:Flavonoids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D044949:Kaempferols / Q000737:chemistry / Q000493:pharmacokinetics; D059625:Liquid-Liquid Extraction / Q000379:methods; D031625:Morus / Q000737:chemistry*; D010936:Plant Extracts / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D018515:Plant Leaves / Q000737:chemistry; D010949:Plasma / Q000737:chemistry*; D011794:Quercetin / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012431:Rutin / Q000737:chemistry / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D005419:Flavonoids; D044949:Kaempferols; D010936:Plant Extracts; C047368:3-methylquercetin; C016527:isoquercitrin; D012431:Rutin; D011794:Quercetin; C001579:astragalin
keywords: Flavonoids; LC–MS/MS; Metabolites; Mulberry leaves; Pharmacokinetics