Rapid quantification of bile acids in serum by LC-MS/MS and application to serum bile acid profile in voriconazole administered patients with invasive fungal infections

Objectives Disruption of bile acid homeostasis is implicated in the pathogenesis and progress of several liver diseases, including drug-induced liver injury (DILI). A rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying 30 bile acids in human serum was developed and applied to analyze serum bile acid profile in voriconazole administered patients with invasive fungal infections.Methods The stable isotope-coded bile acids were used as internal standards. The analytes in serum samples (50 μL) were extracted by protein precipitation and isolated by a Kinetex EVO C18 column (50 × 2.1 mm, 2.6 μm). The detection was performed using multiple reaction monitoring (MRM) in electrospray negative ionization mode.Results All of the 30 bile acids were sufficiently separated within 10 min with good linearity (r > 0.99) over tested calibration ranges. The accuracy and precision values were in the range of 85.42–114.3% and 1.8–13.8%, respectively. The matrix effect, recovery, stability, and dilution integrity all met the acceptance criteria. Serum bile acid profile changed in patients with supratherapeutic voriconazole concentration (>10 μg/mL).Conclusions This LC-MS/MS method for the quantification of 30 bile acids in human serum might apply a new analytical approach for liver function evaluation.