A Sensitive Liquid Chromatography-Mass Spectrometry Method for Determination of Toosendanin in Rat Plasma and its Application to Pharmacokinetic Study

作者：Shen, Chuangpeng; Pan, Zhisen; Wu, Xiaojie; Zhong, Chong; Li, Qiao; Si, Yuqi; Liu, Changhui; Tu, Haitao; Deng, Zhijun; Zhu, Zhangzhi^*; Guo, Jiewen^*; Xin, Xiaoyi^*; Liu, Min^*

来源：Journal of Chromatographic Science, 2022, 60(5): 478-485.

DOI：10.1093/chromsci/bmab135

• TOXIN TYPE-A
• INSECTICIDE
• MELIACEAE
• BOTULISM
• GROWTH
• CANCER
• CELLS

A simple, rapid and sensitive analytical method was developed for the determination of toosendanin in rat plasma using liquid chromatography tandem mass spectrometry (LC-MS/MS). Andrographolide was selected as the internal standard, and the plasma samples were extracted by liquid-liquid extraction with diethyl ether. Chromatographic separation was performed on a Dikma Spursil C18, 3.5 mu m (150 x 2.1 mm i.d) analytical column with 85% methanol:water (v/v) containing 0.025% formic acid (pH = 3.9) as mobile phase. The flow rate was 0.25 mL/min, and the total run time was 3 min. Detection was performed with a triple-quadrupole tandem mass spectrometer using negative ion mode electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. The MS/MS ion transitions monitored were m/z 573.1 -> 531.1 and 349.0 -> 287.0 for toosendanin and andrographolide, respectively. Good linearity was observed over the concentration range of 3.125-500 ng/mL in 100 mu L of rat plasma with a correlation coefficient >0.9997. Intra- and inter-assay variabilities were <8.5% in plasma. The recovery and the matrix effect were in the range 71.8-73.5% and 96.4-103.8%, respectively. The analyte was stable under various conditions (at room temperature, during freeze-thaw settings, in the autosampler, and under deep-freeze conditions). The method was successfully applied to a pharmacokinetic study of toosendanin after its oral administration in rats at a dose of 10 mg/kg.

• 单位
  1; Guangzhou University of Chinese Medicine