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  • P-ISSN 1225-0163
  • E-ISSN 2288-8985

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    Liquid chromatography-tandem mass spectrometric analysis of oleracone D and its application to pharmacokinetic study in mice

    Analytical Science and Technology / Analytical Science and Technology, (P)1225-0163; (E)2288-8985
    2021, v.34 no.5, pp.193-201
    https://doi.org/10.5806/AST.2021.34.5.193
    Dong Yu Lim (College of Pharmacy, Dankook University)
    Tae Yeon Lee (College of Pharmacy, Dankook University)
    Jaehyeok Lee (Kyungpook National University)
    Im-Sook Song (Kyungpook National University)
    Young Taek Han (College of Pharmacy, Dankook University)
    Min-Koo Choi (College of Pharmacy, Dankook University)
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    Abstract

    We have demonstrated a sensitive analytical method of measuring oleracone D in mouse plasma using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oleracone D and oleracone F (internal standard) in mouse plasma samples were processed using a liquid-liquid extraction method with methyl tertbutyl ether, resulting in high and reproducible extraction recovery (80.19-82.49 %). No interfering peaks around the peak elution time of oleracone D and oleracone F were observed. The standard calibration curves for oleracone D ranged from 0.5 to 100 ng/mL and were linear with r2 of 0.992. The inter- and intra-day accuracy and precision and the stability fell within the acceptance criteria. The pharmacokinetics of oleracone D following intravenous and oral administration of oleracone D at doses of 5 mg/kg and 30 mg/kg, respectively, were investigated. When oleracone D was intravenously injected, it had first-order elimination kinetics with high clearance and volume of distribution values. The absolute oral bioavailability of this compound was calculated as 0.95 %, with multi-exponential kinetics. The low aqueous solubility and a high oral dose of oleracone D may explain the different elimination kinetics of oleracone D between intravenous and oral administration. Collectively, this newly developed sensitive LC-MS/MS method of oleracone D could be successfully utilized for investigating the pharmacokinetic properties of this compound and could be used in future studies for the lead optimization and biopharmaceutic investigation of oleracone D.

    keywords
    oleracone D, LC-MS/MS, pharmacokinetics, plasma stability, protein binding


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