Simultaneous determination of Maillard reaction impurities in memantine tablets using HPLC with charged aerosol detector.

A gradient high performance liquid chromatographic (HPLC) method using charged aerosol detection (CAD) was developed for the simultaneous determination of impurities formed by the Maillard reaction in memantine tablets. These impurities were a memantine-lactose adduct (ML), a memantine-dimethylamino glycine adduct (DMAG), a memantine-galactose adduct (MGAL), and a memantine-glucose adduct (MGLU). The chromatographic separation was performed on a Synergy Hydro RP column (100 mm×3 mm, 2.5 μm particles) from Phenomenex with gradient elution using mobile phases consisting of 0.6% (v/v) of heptafluorobuturic acid (HFBA) in two acetonitrile-isopropyl alcohol-water mixtures. The method validation for the impurities included linearity, accuracy by spike recovery, precision, limits of detection and quantitation, and robustness. The method was sensitive for these non-chromophoric impurities down to 0.4-0.6 μg/mL (0.02-0.03% of the memantine drug substance). The effect of mobile phase HFBA concentration on chromatographic resolution and peak shape was investigated, and the effect of sample diluent acidification on method accuracy via spike recovery was studied. The operational simplicity of the CAD detector for routine quality control has been demonstrated.