ABSTRACT
Drug-induced liver injury (DILI) is a major cause of drug failure in clinical trial and market withdrawal. Animal models are utilized to predict the risk of drug-induced liver injury. However, due to species differences, the accuracy of animal models is poor. Multiple human-derived hepatotoxic prediction models have been developed to assess this potential risk. This article reviews commonly used in vitro hepatotoxic models, as well as the latest improvement of hepatocyte culture protocols, especially hepatic co-culture system and 3D culture system in order to improve the accuracy of hepatotoxic risk prediction, which may also guide the liver toxicity mechanistic investigation in clinic.
ABSTRACT
Ginseng saponins isolated from ginseng, have been regarded as the principal constituents responsible for the biological activities. The aim of this study was to set up a liquid chromatography-mass spectrometry (LC-MS) method for simultaneously determine the concentration of Ginsenoside Rg1 and its secondary glycoside Rh1 and aglycone protopanaxatriol (PPT) in rat plasma so as to study the pharmacokinetics of Rg(1) after intraveneous (i.v.) and intragastric gavage (i.g.) administration. One hundred microliters or 1.0 ml of rat plasma samples from i.v. or i.g. treated rats were used respectively for analysis. After solid-phase extraction (SPE) and high performance liquid chromatography (HPLC) separation, the chloride adduct anions [M+Cl]- of Rg1, Rh1 and PPT were analyzed by LC-MS in selected ions monitoring (SIM) mode. Rg(1) could be determined by this LC-MS method over the ranges of 1.56-250 ng/ml and 250-20,000 ng/ml with the correlation coefficients of 0.999 and 0.9998, respectively. The detection limits (LOD) of this method was 20 pg (S/N>3) for Rg1, 100 pg for Rh1 and 10 pg for PPT. Chromatographic separation was achieved in less than 8 mins. The method has been used for the pharmacokinetic study of Rg1 in rats.
