Determination of 14 Bile Acids in Human Plasma by LC-MS/MS and Its Application in Research of Hepatotoxicity Induced by Cyclosporine A / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish a method for simultaneous quantitative determination of 14 bile acids in human plasma by liquid chromatograohy-tandem mass spectrometry (LC-MS/MS) and to explore the correlation between the hepatotoxicity induced by cyclosporine A and bile acids. METHODS: Plasma samples were extracted by protein precipitation and bile acids were separated on a Waters ACQUITY UPLC HSS T3(2.1 mm×150 mm,1.8 μm) column with a flow rate of 0.3 mL•min-1. The mobile phase was water (containing 4 mmol•L-1 ammonium acetate) and 95% acetonitrile using gradient elution in 15 min. The detection system used an electrospray ion source in negative ion mode. RESULTS: Fourteen bile acids had a good linear relationship, the intra-and inter-assay RSD values were less than 15%, the accuracy was between 87% and 116%, and the extraction recovery rates of the quality was between 101% and 120%. The concentration of cholic acid (CA) was well correlated with cyclosporine A and suggested that bile acids may be associated with the hepatotoxicity induced by cyclosporine A. CONCLUSION: This LC-MS/MS method for quantitatively determining various bile acids in human plasma is convenient, accurate and sensitive and can be used for further basic research in hepatotoxicity caused by cyclosporine A.