Establishment of UPLC‐MS/MS Method for Determining the Content of Memantine in Rat Plasma and Its Pharmacokinetic Differences at Different Altitudes

This study aimed to establish an UPLC-MS/MS method for determining memantine (MM) in rat plasma and to investigate its pharmacokinetic variations at different altitudes. MM was separated on a Hypersil Gold C18 column using a gradient elution method and detected by selected reaction monitoring (SRM). Sixteen fasted SD rats were randomized into low- and high-altitude groups (n = 8 each) and orally administered MM at 5 mg/kg. Serial blood samples were collected at 0-, 0.08-, 0.25-, 0.5-, 0.75-, 1-, 2-, 4-, 8-, 12-, 24-, 36-, and 48-h postdose for pharmacokinetic analysis. Compared with the low-altitude group, the high-altitude group exhibited a 72.15% increase in the area under the plasma concentration-time curve (AUC(0-∞)), a 39.97% reduction in apparent volume of distribution (Vz/F), the apparent clearance (CLz/F) decreased by 41.99%, the peak concentration (Cmax) increased by 131.52%, while the half-life (t_1/2) and time to peak concentration (Tmax) showed no significant changes. In conclusion, high-altitude hypoxia significantly affects MM metabolism in rats, potentially posing a risk of drug accumulation in plasma. The research findings provide a reference for the rational use of MM in high-altitude regions.