Simultaneous quantification of donepezil and memantine by HPLC-refractive index detection for novel drug delivery systems.

Alzheimer's dementia is often treated with a combination of memantine and donepezil, which is more effective than monotherapy. Despite its clinical relevance, simultaneous determination is challenging due to the absence of a chromophore in memantine. Herein, a simple, accurate, and sensitive High-Performance Liquid Chromatography-refractive index method is reported for the first time for the simultaneous quantification of memantine and donepezil for routine analysis. The method employed a C18 column with a mobile phase of 1% diethylamine in water: methanol (50:50, v/v), adjusted to pH 6.0 using dilute glacial acetic acid. Optimized conditions (flow rate 0.8 mL/min, injection volume 20 µL at 40 °C) yielded a linearity ranging between 2.5 and 30 µg/mL (R² = 1) for both the drugs. Limits of detection and quantification were 0.194 and 0.589 µg/mL for Dnp and 0.237 and 0.718 µg/mL for Mem. Validation confirmed precision, robustness, and stability. The method was successfully applied to determine the amount of drug release from the intranasal nano-colloidal preparations, along with optimized sample preparations giving analyte recoveries within range without any interference from the formulation excipients. The derivatization exhibited acceptable selectivity with no interfering peaks from excipients, demonstrating its suitability for routine analysis. The sustainability of the developed method was assessed using different metrics, namely the Analytical GREEnness Metric Approach and Software, Green Analytical Procedure Index, and Blue Applicability Grade Index.