Development of a Rapid and Sensitive LC-MS/MS assay for the Determination of Sorafenib in Human Plasma

摘要

A rapid and sensitive liquid chromatography/tandem mass spectrometric (LC/MS/MS) assay was developed for the quantitative determination of sorafenib in human plasma. Sample pretreatment involved simple protein precipitation by the addition of 0.5 mL acetonitrile, containing internal standard ([²H3, ¹⁵N] sorafenib), to 50 μL of plasma sample volume. Separation was achieved on a Waters SymmetryShield RP8 (2.1×50 mm, 3.5 μm) column at room temperature using an isocratic elution method with acetonitrile/0.1% formic acid in water: 65/35 (v/v) at a flow rate of 0.25 mL/min. Detection was performed using electrospray ionization in positive ion Multiple Reaction Monitoring (MRM) mode by monitoring the ion transitions from m/z 464.9→ 252.0 (sorafenib) and m/z 469.0→259.0 (internal standard). Calibration curves were linear in the concentration range of 5–2000 ng/mL. The accuracy and precision values, calculated from three different sets of quality control samples analyzed in quintuplicate on six different days, ranged from 92.86–99.88 % and from 1.19–4.53 %, respectively.