A rapid and sensitive LC-MS/MS method was developed and fully validated for the determination of obeticholic acid in human plasma. Glimepiride was used as internal standard. For this method, liquid-liquid extraction was performed to extract analyte from the plasma samples. Chromatographic separation was performed on a C18 (2.1 × 50 mm, 2.7 μm, Agilent) column with isocratic elution using water containing 0.1% formic acid and acetonitrile containing 0.1% formic acid at a flow rate of 0.4 mL/min. The mass detection was performed in negative mode. The precursor-product ion pairs for MRM were m/z 465.3 → 419.3 for obeticholic acid and m/z 489.3 → 224.8 for the IS. The method exhibited great linearity over the concentration range of 0.150-100 ng/mL for obeticholic acid. The sensitivity, linearity, accuracy, precision, recovery, matrix effect and stability of this method were all within the acceptable limits. The method was successfully validated and applied to the pharmacokinetic studies in healthy Chinese volunteers after a single oral dose administration of obeticholic acid tablets of 10 mg, and the pharmacokinetic characteristics of obeticholic acid in human were reported for the first time.
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