Quantitative Determination of Myricetin in Rat Plasma by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry and its Absolute Bioavailability

Y. Dang; G. Lin; Y. Xie; J. Duan; P. Ma; G. Li; G. Ji

doi:10.1055/s-0033-1363220

Drug Research, Inhaltsverzeichnis

Drug Res (Stuttg) 2014; 64(10): 516-522
DOI: 10.1055/s-0033-1363220

Original Article

Quantitative Determination of Myricetin in Rat Plasma by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry and its Absolute Bioavailability

Y. Dang

¹Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai, China

,

G. Lin

¹Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai, China

,

Y. Xie

¹Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai, China

,

J. Duan

²Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China

,

P. Ma

³Global Pharmaceutical Research and Development, Hospira Inc., McPherson, KS, USA

,

G. Li

⁴Pharmacy Department, Shanghai TCM-integrated Hospital, Shanghai, China

,

G. Ji

²Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China

› Institutsangaben

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.

Key words

UPLC-MS/MS - myricetin - rat plasma - pharmacokinetics - absolute bioavailability

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Referenzen

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