QUANTITATIVE DETERMINATION OF MEMANTINE IN HUMAN PLASMA BY LIQUID CHROMATOGRAPHY–TANDEM MASS SPECTROMETRY: APPLICATION TO A BIOEQUIVALENCE STUDY.

A simple, sensitive, and rapid liquid chromatography-tandem mass spectrometry method for determination of memantine in human plasma was established. A one-step protein precipitation with methanol was used to extract the analyte from plasma samples. Memantine and amantadine (internal standard, IS) were separated on a YMC-ODS-C18 column using 0.1% formic acid and methanol as a mobile phase at a flow rate of 0.3 mL/min. Detection was performed on positive ion mode of the transitions at 180.3→107.3 for memantine and 152.2→135.3 for IS by selected reaction monitoring (SRM). The assay was validated over the concentration range of 0.5–50 ng/mL with a lower limit of quantification (LLOQ) of 0.5 ng/mL. The intra- and inter-batch precision (RSD) were no more than 5.96% and 6.37%, respectively. The accuracy was from −3.02% to 7.74%. The validated method was successfully applied to a randomized, 2-period cross-over bioequivalence study in 22 healthy Chinese volunteers following a single oral dose of 10 mg memantine hydrochloride tablet. The simple, inexpensive protein precipitation and high-throughput method makes it a suitable and valuable tool in the investigation of the clinical pharmacokinetics and bioequivalence. [ABSTRACT FROM PUBLISHER]