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DOI: 10.1055/s-0033-1363220
Quantitative Determination of Myricetin in Rat Plasma by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry and its Absolute Bioavailability
Publikationsverlauf
received 29. September 2013
accepted 25. November 2013
Publikationsdatum:
19. Dezember 2013 (online)
![](https://www.thieme-connect.de/media/drugres/201410/lookinside/thumbnails/10.1055-s-0033-1363220-1.jpg)
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.
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References
- 1 Wang SJ, Tong Y, Lu S et al. Anti-inflammatory activity of myricetin isolated from Myrica rubra Sieb. Et Zucc leaves. Planta Med 2010; 76: 1492-1496
- 2 Tiwari R, Mohan M, Kastur S et al. Cardioprotective potential of myricetin in isoproterenol-induced myocardial infarction in Wistar rats. Phytother Res 2009; 23: 1361-1366
- 3 Gao H, Kuroyanagi M, Wu L et al. Antitumor-promoting constituents from Dioscorea bulbifera L. in JB6 mouse epidermal cells. Biol Pharm Bull 2002; 25: 1241-1243
- 4 Sahreen S, Khan MR, Khan RA. Hepatoprotective effects of methanol extract of Carissa opaca leaves on CCl4-induced damage in rat. BMC Complement Altern Med 2011; 11: 48
- 5 Sumino M, Sekine T, Ruangrungsi N et al. Ardisiphenols and other antioxidant principles from the fruits of Ardisia colorata. Chem Pharm Bull 2002; 50: 1484-1487
- 6 Jeong CH, Choi GN, Kim JH et al. Protective effects of aqueous extract from Cudrania tricuspidata on oxidative stress-induced neurotoxicity. Food Sci Biotechnol 2010; 19: 1113-1137
- 7 Hakkinen SH, Karenlampi SO, Heinonen IM et al. Content of the flavonols quercetin, myricetin, and kaempferol in 25 edible berries. J Agric Food Chem 1999; 47: 2274-2279
- 8 German JB, Walzem RL. The health benefits of wine. Annu Rev Nutr 2000; 20: 561-593
- 9 Wang L, Lee IM, Zhang SM et al. Dietary intake of selected flavonols, flavones, and flavonoid-rich foods and risk of cancer in middle-aged and older women. Am J Clin Nutr 2009; 89: 905-912
- 10 Gordon MH, Roedig-Penman A. Antioxidant activity of quercetin and myricetin in liposomes. Chem Phys Lipids 1998; 97: 79-85
- 11 Mahjoub MA, Ammar S, Edziri H et al. Anti-inflammatory and antioxidant activities of some extracts and pure natural products isolated from Rhus tripartitum (Ucria). Med Chem Res 2010; 19: 271-282
- 12 Phillips PA, Sangwan V, Borja-Cacho D et al. Myricetin induces pancreatic cancer cell death via the induction of apoptosis and inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Cancer Lett 2011; 308: 181-188
- 13 Naz S, Siddiqi R, Ahmad S et al. Antibacterial activity directed isolation of compounds from Punica granatum. J Food Sci 2007; 72: M341-345
- 14 Scarabelli TM, Mariotto S, Abdel-Azeim S et al. Targeting STAT1 by myricetin and delphinidin provides efficient protection of the heart from ischemia/reperfusion-induced injury. FEBS Lett 2009; 583: 531-541
- 15 Zern TL, Wood RJ, Greene C et al. Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress. J Nutr 2005; 135: 1911-1917
- 16 Panickar KS, Anderson RA. Mechanisms underlying the protective effects of myricetin and quercetin following oxygen-glucose deprivation-induced cell swelling and the reduction in glutamate uptake in glial cells. Neuroscience 2011; 183: 1-14
- 17 Liu IM, Tzeng TF, Liou SS et al. Myricetin, a naturally occurring flavonol, ameliorats insulin resistance induced by a high-fructose diet in rats. Life Sci 2007; 81: 1479-1488
- 18 Delgado ME, Haza AI, Garcia A et al. Myricetin, quercetin, (+)-catechin and (-)-epicatechin protect against N-nitrosamines-induced DNA damage in human hepatoma cells. Toxicol In Vitro 2009; 23: 1292-1297
- 19 Du FY, Xiao XH, Li GK. Ionic liquid aqueous solvent-based microwave-assisted hydrolysis for the extraction and HPLC determination of myricetin and quercetin from Myrica rubra leaves. Biomed Chromatogr 2011; 25: 472-478
- 20 Beevi SS, Narasu ML, Gowda BB. Polyphenolics profile, antioxidant and radical scavenging activity of leaves and stem of Raphanus sativus L. Plant Foods Hum Nutr 2010; 65: 8-17
- 21 Zhang YS, Zhang QY, Li LY et al. Simultaneous determination and pharmacokinetic studies of dihydromyricetin and myricetin in rat plasma by HPLC-DAD after oral administration of Ampelopsis grossedentata decotion. J Chromatogr B 2007; 860: 4-9
- 22 Biesaga M. Influence of extraction methods on stability of flavonoids. J Chromatogr A 2011; 1218: 2505-2512
- 23 Lin Y, Wu B, Li Z et al. Metabolite identification of myricetin in rats using HPLC coupled with ESI-MS. Chromatographia 2012; 75: 655-660
- 24 Guo J, Xue C, Duan J et al. Fast characterization of constituents in HuangKui capsules using UPLC-QTOF-MS with collision energy and mass fragment software. Chromatographia 2011; 73: 447-456
- 25 U.S. Food and Drug Administration . FDA Guidance for industry: Bioanalytical Method Validation. U.S. Department of Health and Human Services, Food and Drug Administration. Center for Drug Evaluation and Research: Rockville 2001;
- 26 Zhao Y, Wang L, Bao Y et al. A sensitive method for the detection and quantification of ginkgo flavonols from plasma. Rapid Commun Mass Spectrom 2007; 21: 971-981
- 27 Walle T, Otake Y, Walle UK et al. Quercetin glucosides are completely hydrolyzed in ileostomy patients before absorption. J Nutr 2000; 130: 2658-2661
- 28 Shia CS, Tsai SY, Lin JC et al. Steady-state pharmacokinetics and tissue distribution of anthraquinones of Rhei Rhizoma in rats. J Ethnopharmacol 2011; 137: 1388-1394
- 29 Shia CS, Hou YC, Juang SH et al. Metabolism and pharmacokinetics of san-huang-xie-xin-tang, a polyphenol-rich chinese medicine formula, in rats and ex-vivo antioxidant activity. Evid Based Complement Alternat Med 2011; 721293
- 30 Ding Y, Peng M, Zhang T et al. Quantification of conjugated metabolites of drugs in biological matrices after the hydrolysis with β-glucuronidase and sufatase: a review of bio-analytical methods. Biomed Chromatogr 2013; 27: 1280-1295
- 31 Barve A, Chen C, Hebbar V et al. Metabolism, oral bioavailability and pharmacokinetics of chemopreventive kaempferol in rats. Biopharm Drug Dispos 2009; 30: 356-365
- 32 Li GW, Zeng XL, Xie Y et al. Pharmacokinetic properties of isorhamnetin, kaempferol and quercetin after oral gavage of total flavones of Hippophae rhamnoides L. in rats using a UPLC-MS method. Fitoterapia 2012; 83: 182-191