A simple and rapid liquid chromatography–tandem mass spectrometry method for the simultaneous determination of 15 bile acids in human serum and its application to patients with decompensated cirrhosis

Abstract

Liver cirrhosis is currently the twelfth leading cause of death globally and the sixth leading cause of death in China. Its treatment is expensive. Changes in the composition of the serum bile acid pool are sensitive indicators of the severity of liver cirrhosis. In this study, a novel LC-tandem mass spectrometry (LC-MS/MS) method was developed and used to simultaneously determine 15 bile acids in human serum in patients with decompensated cirrhosis. Sample preparation involved spiking with isotope internal standards followed by protein precipitation. The analytical run time was 5 min. The LC-MS/MS method was fully validated according to Clinical and Laboratory Standards Institute (CLSI) C62A and the consensus of method development and validation of liquid chromatography-tandem mass spectrometry in clinical laboratories.The method achieved an acceptable coefficient of variation for precision (0.83%-14.80%) and accuracy (89.39%-107.62%). Finally, as proof of applicability, the method was applied to patients with decompensated cirrhosis in routine clinical sample analysis. The degree of variation of different bile acids was clearly shown. These results indicated that abnormal metabolic pathways might play important roles in decompensated cirrhosis.bile acids, decompensated cirrhosis, human serum, LC-MS/MS | INTRODUCTIONLiver cirrhosis is now the twelfth leading cause of death worldwide and the sixth leading cause of death in China. The only curative therapy is liver transplantation, which is expensive. As a result, liver cirrhosis remains a global health challenge, despite mass vaccination campaigns to prevent viral hepatitis (Chen et al., 2016;Lozano et al., 2012). Pathologically, liver cirrhosis comprises compensated and decompensated stages. In general, the common end stage of liver disease is decompensated cirrhosis, which has high short-term mortality.Currently, liver biopsy represents the gold standard for the diagnosis and assessment of liver cirrhosis severity. However, the fragility of