Ion-pair reversed-phase HPLC method for determination of sodium tanshinone 2A sulfonate in biological samples and its pharmacokinetics and biodistribution in mice

  • Mao ShengJun
    Key Laboratory of Drug Targeting and Drug Delivery Ministry of Education, West China School of Pharmacy, Sichuan University
  • Jin Hui
    Key Laboratory of Drug Targeting and Drug Delivery Ministry of Education, West China School of Pharmacy, Sichuan University
  • Bi YueQi
    Key Laboratory of Drug Targeting and Drug Delivery Ministry of Education, West China School of Pharmacy, Sichuan University
  • Liang Zhen
    Key Laboratory of Drug Targeting and Drug Delivery Ministry of Education, West China School of Pharmacy, Sichuan University
  • Li Hui
    Department of Hematology, People's Hospital of Sichuan Province
  • Hou ShiXiang
    Key Laboratory of Drug Targeting and Drug Delivery Ministry of Education, West China School of Pharmacy, Sichuan University

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タイトル別名
  • Ion-Pair Reversed-Phase HPLC Method for Determination of Sodium Tanshinone IIA Sulfonate in Biological Samples and Its Pharmacokinetics and Biodistribution in Mice

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説明

The ion-pair reversed-phase HPLC method for determination of sodium tanshinone IIA sulfonate (STS) in various biological samples was for the first time developed and validated, and was applied for pharmacokinetics and tissue distribution studies of intravenously administrated STS in mice. A linear relation was found between peak area and STS concentrations within the ranges of 0.1—5 μg/ml for plasma, 0.1—5 μg/g of tissue for kidney homogenate, 0.1—20 μg/g of tissue for liver homogenate, 0.1—1 μg/g of tissue for heart, spleen and lung homogenates, respectively. In plasma and tissues, the limit of quantification (LOQ) and the limit of detection (LOD) for STS were 100 ng/ml and 20 ng/ml. In all biological specimens, the average inter- and intra-day precision of STS were within 4.9%. The recoveries were more than 92% at all concentration levels in each type of biological specimens. STS plasma concentration–time data were best fitted with a two-compartment model, characterized by an initial rapid phase of drug concentration decrease, and a slower terminal elimination phase. The pharmacokinetics of STS was characterized with a distribution half-life (t1/2α) of 1.2±0.18 min, a terminal half-life (t1/2β) of 21.6±2.4 min, a distribution volume (V) of 0.057±0.011 l/kg, a plasma clearance (CL) of 0.86±0.12 l/h/kg and an AUC0—∞ of 58.41±6.21 μg·h/ml. STS was widely distributed into most tissues and was obviously accumulated in liver. This results indicated that STS may be promising to treat liver disease.

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