Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

Analytica Chimica Acta
Bhowmik Salil KumarByung Hwa Jung

Abstract

In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg(-1) day(-1) or 250 mg kg(-1) day(-1) for a period of 7 days (n=4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were...Continue Reading

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Citations

Dec 6, 2012·Archives of Pharmacal Research·Salil Kumar BhowmikByung Hwa Jung
Nov 15, 2011·Journal of Proteomics·Aihua ZhangXijun Wang
Apr 17, 2015·Mass Spectrometry Reviews·Mona M KhamisAnas El-Aneed
Mar 13, 2014·Biomedical Chromatography : BMC·Zhang LinYizeng Liang
Jun 26, 2015·Metabolomics : Official Journal of the Metabolomic Society·Abdul-Hamid EmwasDavid S Wishart
Jan 4, 2012·Electrophoresis·Véréna PoinsotFrançois Couderc

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