Development of memantine in human plasma by liquid chromatography tandem mass spectrometry

OBJECTIVE To validate a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of memantine in human plasma.METHODS The analyte was separated on a Ultimate XB-C18 column(150 mm 4.6 mm, 5 μm) with a mobile phase of methanol and water containing 0.5% formic acid (70∶30) at a flow rate of 0.5mL·min-1. The multiple reaction monitoring (MRM) mode was used for analyte quantification, and the precursor-to-product ion transition of m/z 180→163 (memantine) and 152→135 (amantadine, IS) were selected, respectively. The plasma sample was liquid-liquid extracted by ethyl acetate. RESULTS The weighted (1/x2) calibration curve was linear in the 0.2-100.0 μg·L-1 range for memantine, and the low limit of quantification was 0.2 μg·L-1. The inter-and intra-day precisions (RSD) were 7. Plasma samples were stable under freezed and freeze-thaw conditions. CONCLUSION The developed LC/MS/MS method was selective, sensitive and simple, and was successfully applied to the pharmacokinetic study of memantine after oral administration to Chinese healthy volunteers.