A selective and sensitive high-performance liquid chromatography-electrospray ionization mass spectrometry method has been developed for the determination of sodium ferulate in human plasma. The sample preparation was a liquid–liquid extraction and chromatographic separation was achieved with an Agilent ZORBAX SB-C18 (3.5 μm, 100 mm × 3.0 mm) column, using a mobile phase of methanol–0.05% acetic acid 40:60 (v/v). Standard curves were linear (r2 = 0.9982) over the concentration range of 0.007–4.63 nM/ml and had acceptable accuracy and precision. The within- and between-batch precisions were within 12% relative standard deviation. The lower limit of quantification (LLOQ) was 0.007 nM/ml. The validated HPLC–ESI-MS method has been used successfully to study sodium ferulate pharmacokinetics, bioavailability and bioequivalence in 20 healthy volunteers.