Determination of duloxetine in human plasma by liquid chromatography with atmospheric pressure ionization-tandem mass spectrometry and its application to pharmacokinetic study.

A rapid, sensitive and accurate liquid chromatographic-tandem mass spectrometry (LC-MS-MS) method is described for the determination of duloxetine in human plasma. Duloxetine was extracted from plasma using methanol and separated on a C18 column. The mobile phase consisting of a mixture of acetonitrile and 5mM ammonium acetate (45:55, v/v, pH 3.5) was delivered at a flow rate of 0.3 ml/min. Atmospheric pressure ionization (API) source was operated in positive ion mode. Multiple reaction monitoring (MRM) mode using the transitions of m/z 298.1-->m/z 44.0 and m/z 376.2-->m/z 123.2 were used to quantify duloxetine and internal standard (I.S.), respectively. The linearity was obtained over the concentration range of 0.1-50.0 ng/ml and the lower limit of quantitation (LLOQ) was 0.1 ng/ml. This method was successfully applied to pharmacokinetic study of a duloxetine formulation product after oral administration to healthy human subjects.