Ultra High Performance Liquid Chromatography Coupled with Q Exactive Hybrid Quadrupole-orbitrap Mass Spectrometry for Serumal Metabonomics Study of Drug-induced Liver Injury in Patients / 分析化学

ABSTRACT

Ultra high performance liquid chromatography coupled with a Q Exactive hybrid quadrupole-orbitrap mass spectrometry ( UPLC-MS/MS) and multivariate statistical analysis was applied to metabonomic study of drug-induced liver injury. This investigation focused on the liver injury in clinic which was induced by antitumor drug, traditional Chinese medicine, statins and antibiotics. After precipitated by cold acetonitrile, the serum samples were separated on a HSS T3-C18 column using water (containning 0. 01% formic acid) and acetonitrile as mobile phase by gradient elution. Based on metabonomic profiles analysis of the orthogonal projections to latent structures discriminant analysis ( OPLS-DA ) and partial least squares-discriminant analysis ( PLS-DA) , 114 endogenous metabolites had been found to have significant differences between drug-induced liver injury patients and healthy volunteers, 38 endogenous metabolites have significant difference (p<0. 001). According to the results of the OPLS-DA, MS/MS data and human metabolome database ( HMDB) , phenylalanine and dimethylguanosine had been identified as potential biomarkers related to drug-induced liver injury for early discovery and diagnosis.