Determination of concentrations and toxicokinetics of triptolide in plasma and liver of mice by UHPLC-MS/MS.
10.19540/j.cnki.cjcmm.20220507.501
- Author:
Guo-Qing LI
1
;
Ting SHU
2
;
Yuan-Yuan CHAI
2
;
Xin HUANG
2
;
Zhen-Zhou JIANG
2
;
Lu-Yong ZHANG
3
Author Information
1. New Drug Research and Development Center, Guangdong Pharmaceutical University Guangzhou 510006, China.
2. New Drug Screening Center, Jiangsu Center for Pharmacodynamics Research and Evaluation,China Pharmaceutical University Nanjing 210009, China.
3. New Drug Research and Development Center, Guangdong Pharmaceutical University Guangzhou 510006, China New Drug Screening Center, Jiangsu Center for Pharmacodynamics Research and Evaluation,China Pharmaceutical University Nanjing 210009, China.
- Publication Type:Journal Article
- Keywords:
hepatotoxicity;
toxicokinetics;
triptolide(TP)
- MeSH:
Animals;
Chromatography, High Pressure Liquid/methods*;
Diterpenes;
Epoxy Compounds;
Liver;
Mice;
Phenanthrenes;
Tandem Mass Spectrometry/methods*;
Toxicokinetics
- From:
China Journal of Chinese Materia Medica
2022;47(15):4183-4189
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to establish an ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method for determining the concentrations of triptolide(TP) in plasma and liver, and to explore the toxicokinetics of TP and the relationship between TP exposure and liver injury in C57 BL/6 mice, so as to provide reference for dissecting the toxicity mechanism of TP. The liquid chromatography was conducted with ZORBAX SB-C_(18) column(3.0 mm×100 mm, 3.5 μm) and the mobile phase of methanol-0.05 mmol·L~(-1) ammonium acetate. Electrospray ionization(ESI) and multiple reaction monitoring(MRM) mode were employed for mass spectrometry. After oral administration of TP(toxic dose 600 μg·kg~(-1)), the blood and liver tissues of the C57 BL/6 mice were collected at different time points to measure the TP concentrations in plasma and liver tissues. Furthermore, the blood biochemical indexes, including alkaline phosphatase(ALP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), and total bile acid(TBA), were determined. After being processed by DAS 2.0, the experiment data showed that the TP in mice had the toxicokinetic parameters of T_(max)=5 min, C_(max)=14.38 ng·mL~(-1), t_(1/2)=0.76 h, AUC_(0-t)=5.63 h·ng·mL~(-1), MRT_(0-t)=0.56 h, and CL_(Z/F)=103.19 L·h~(-1)·kg~(-1). The trend of TP concentration in mouse liver tissue was consistent with that in plasma. The concentration of TP peaked at the time point of 5 min and then decreased until TP was completely metabolized. The plasma biochemical indexes(ALT, AST, ALP, and TBA) showed no significant changes within 3 h after TP administration. TP had high clearance rate and short residence time and did not significantly increase the blood biochemical indexes in mice. The results suggested that the exposure amount of free TP in vivo cannot directly cause liver injury, which might be caused by the binding of TP to some substances or the stimulation of inflammation and immune response.
