Quantitative determination of myricetin in rat plasma by ultra performance liquid chromatography tandem mass spectrometry and its absolute bioavailability

Drug Res (Stuttg). 2014 Oct;64(10):516-22. doi: 10.1055/s-0033-1363220. Epub 2013 Dec 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Animals
  • Biological Availability
  • Calibration
  • Chromatography, Liquid* / standards
  • Flavonoids / administration & dosage
  • Flavonoids / blood*
  • Flavonoids / pharmacokinetics*
  • Limit of Detection
  • Linear Models
  • Male
  • Rats, Sprague-Dawley
  • Reference Standards
  • Reproducibility of Results
  • Spectrometry, Mass, Electrospray Ionization* / standards
  • Tandem Mass Spectrometry* / standards

Substances

  • Flavonoids
  • myricetin