Home
Resources
Publications
Discovery of Safety Biomarkers for Atorvastatin in Rat Urine Using Mass Spectrometry Based Metabolomics Combined With Global and Targeted Approach

Discovery of Safety Biomarkers for Atorvastatin in Rat Urine Using Mass Spectrometry Based Metabolomics Combined With Global and Targeted Approach

Bhowmik Salil Kumar, Young-Joo Lee, Hong Jae Yi, Bong Chul Chung, Byung Hwa Jung

Anal Chim Acta. 2010 Feb 19;661(1):47-59.

PMID: 20113715

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 compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1105067886	Atorvastatin Related Compound E		1105067-88-6	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: