OBJECTIVE To establish a high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS) method for the determination of fenofibrate acid concentration in human breast milk and to evaluate its clinical application.

METHODS Fenofibrate acid-D6 was used as internal standard and protein precipitation was used for pretreatment of human breast milk, followed by separation on an ACE Excel 3 C₁₈(100 mm×2.1 mm, 3 μm) column with gradient elution of formic acid solution(formic acid∶water=0.1∶100) and methanol. The flow rate was 0.4 mL·min⁻¹, injection volume was 1.0 μL and analysis time was 5 min. The detection of the analytes was performed by electrospray ionization in positive mode by multiple reaction monitoring with the transition of m/z 319.1→233.1(fenofibrate acid) and m/z 325.3→233.0(internal standard). The established LC-MS/MS method was researched in methodology and used to determine the fenofibrate acid concentrations in the human breast milk of 5 lactating patients.

RESULTS The linear range of fenofibrate acid was 1–500 ng·mL⁻¹(r²=0.9988). The RSD of intra-assay and inter-assay precisions of quality control samples were both≤5.78%. The mean recovery and matrix effect were 96.74%–108.50% and 101.01%–102.70%, respectively. This method was successfully applied to the determination of fenofibrate acid concentration in breast milk of 5 lactating patients. The result showed that fenofibrate acid concentration ranged from 8.38 to 442.00 ng·mL⁻¹ in the first breast milk sample, and 2.67 to 60.63 ng·mL⁻¹ on day 5 after fenofibrate withdrawal.

CONCLUSION This established method for quantification of fenofibrate acid in human milk is simple, economical and sensitive, which can help to evaluate the safety of fenofibrate use during lactation.