Drug-induced hepatotoxicity: application of mass spectrometry based metabonomics

Abstract

Drug-induced hepatotoxicity (DIH) is an unpredictable and frequent event with the risk of a life threatening clinical course when it occurs. The detection of hepatotoxic effects is a continuous process covering all drug development phases. Various in vitro liver models have been developed in the past years. However, the high chemical diversity of biological samples and sample's characteristics make the prospect of detecting DIH a difficult and complicated process. Therefore, a good understanding of toxic effects of drugs on the liver and the viability of the experimental models as the main source of samples are essential platforms which are needed for any analytical technique. Major analytical techniques such as hyphenated systems, e.g. chromatography and mass spectrometry (MS) play a pivotal role in the detection of DIH. Nevertheless, these state of the art techniques are not without limitations. This review focuses on highlighting the main aspects of DIH; the applications of mass spectrometry based metabonomics, their applicability with regard to sample availability and comparison with standard clinical chemistry applications. We also propose an approach to study DIH in the early phase of drug discovery. The aim of this paper is foremost to provide an overview and guidance to study and facilitate further discussions on this topic.

Hepatotoxicity and nephrotoxicity assessment on ethanol extract of Fructus Psoraleae in Sprague Dawley rats using a UPLC–Q‐TOF–MS analysis of serum metabolomics

“…Metabolomics, a sensitive and unbiased analytic method, has become a powerful method to identify new biomarkers in many fields, such as toxicology, disease diagnosis, and therapeutic efficacy (Beger et al, 2010; Xuan et al, 2011). The application of metabolomics has been reported in many excellent papers on the evaluation of nephrotoxicity and hepatotoxicity (Dahab & Smith, 2012). Furthermore, it is used for discovering disease biomarkers in clinical chemistry and for understanding pharmacological mechanism and material basis of TCMs (Feng et al, 2018).…”

Principal Component Analysis with Linear and Quadratic Discriminant Analysis for Identification of Cancer Samples Based on Mass Spectrometry

“…[7][8][9] MS is usually coupled with chromatography such as liquid chromatography (LC-MS) and gas chromatography (GC-MS). Other techniques such as surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) are often used in MS applications, including disease screening and diagnosis.5 Some examples of MS applications includes toxicology screening and toxic drug quantification using quadrupole MS/MS; 10 identification of inborn errors in metabolism or genetic defects in newborns for prenatal screening programs using electrospray tandem MS; 11 detection of drug-induced hepatotoxicity using MS-based metabolomics; 12 and identification and quantification of bleomycin in serum and tumor tissue by high resolution LC-MS. 13 MS-based techniques have been largely employed for cancer identification, such as for breast cancer, 14 prostate cancer, 15,16 ovarian cancer, 17 lung cancer, 18 and pancreatic cancer; 19 as well as for identifying many biomarkers. 18,[20][21][22][23][24] One of the main fields using MS data is metabolomics, which aims to identify and quantify small molecules involved in metabolic reactions.…”