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Alzheimer's dementia management often relies on combining memantine and donepezil. However, researchers face difficulties with donepezil and memantine quantification due to memantine’s lack of a chromophore. A new study introduces a simplified HPLC-refractive index (RI) method to solve this analytical hurdle.
Furthermore, this simplified approach utilizes a C18 column with a specific mobile phase of water and methanol. Moreover, the researchers adjusted the mobile phase to pH 6.0 using dilute glacial acetic acid. Consequently, the system achieved perfect linearity for both compounds during the testing phase. Specifically, the method addresses the absence of a chromophore in memantine without needing complex derivatization. Additionally, the validation process confirmed high precision, robustness, and stability for routine use. Notably, the team applied this technique to intranasal nano-colloidal preparations successfully. As a result, the analytical process remains sustainable and environmentally friendly according to green metrics. In addition, the results demonstrated no interference from common formulation excipients during recovery. Therefore, this protocol is highly suitable for routine analysis in modern pharmaceutical settings.
The success of this method supports the development of novel drug delivery systems. Because intranasal preparations offer direct brain targeting, precise quantification becomes essential. Consequently, clinicians may soon see more efficient combination therapies for dementia. This research bridges the gap between complex chemistry and practical clinical application. Future studies will likely build upon these green analytical techniques to improve patient outcomes in geriatrics.
Memantine lacks a chromophore, which means it does not absorb ultraviolet light effectively. This characteristic makes traditional UV detection difficult for simultaneous analysis with donepezil.
The RI method detects compounds based on changes in the refractive index rather than light absorption. Therefore, it allows for the simultaneous donepezil and memantine quantification without complex chemical pre-treatments.
Disclaimer: This content is for informational and educational purposes only. It does not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare provider with any questions you may have regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.
References
Singh B et al. Simultaneous quantification of donepezil and memantine by HPLC-refractive index detection for novel drug delivery systems. BMC Chem. 2026 May 25. doi: 10.1186/s13065-026-01835-9. PMID: 42185915.
Atri A. Donepezil and memantine combination therapy in Alzheimer's disease. Drugs Aging. 2013;30(10):783-804.
Howard R, et al. Donepezil and memantine for moderate-to-severe Alzheimer's disease. N Engl J Med. 2012;366(10):893-903.

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A new green HPLC-RI method enables the simultaneous quantification of donepezil and memantine for advanced intranasal drug delivery in Alzheimer's disease....
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