We developed a method for the determination of milnacipran in serum using a system combining liquid chromatography and mass spectrometry (LC/MS) in which electrospray ionization (ESI) was used. Milnacipran was extracted from serum by liquid-liquid extraction using an Extrelut® NT 3 column. The chromatographic separations of milnacipran and amoxapine (internal standard) were performed using a XTerra® RP 18 (150 × 2.1 mm I.D.) column with a gradient of 0.1% formic acid and 0.1% formic acid in acetonitrile as the mobile phase. The extraction recoveries at concentrations of 10 and 100 ng/mL were 85.6 and 83.7%, respectively. The calibration curve was linear in a concentration range from 5 to 300 ng/mL and the detection limit was 1 ng/mL. The intra-day and inter-a day assay precision expressed as coefficients of variation (C.V.) were 1.94-2.17% and 5.75-6.20%, respectively. This method proved to be useful in quantifying milnacipran in serum obtained from a patient who took this drug.
