A COMPREHENSIV REVIEW ON ANALYTICAL METHODS FOR ESTIMATION OF DEXTROMETHORPHAN HYDROBROMIDE AND MEMANTINE HYDROCHLORIDE

Dextromethorphan hydrobromide (DXM HBr) and memantine hydrochloride (MEM HCl) are two pharmacologically significant central nervous system (CNS) agents that have attracted considerable interest due to their neuroprotective potential. DXM, a dextrorotatory morphinan derivative, is primarily used as a non-opioid antitussive but also exhibits uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonism and sigma-1 receptor agonism, positioning it as a candidate in epilepsy, neuropathic pain, and neurodegenerative disorders. MEM HCl, a low-to-moderate affinity NMDA receptor antagonist, selectively blocks pathological glutamatergic excitotoxicity while preserving physiological neurotransmission, making it an approved therapy for moderate to severe Alzheimer’s disease. The combination of DXM and MEM has been explored for synergistic neuroprotection, further emphasizing the need for reliable analytical methodologies. Over the past two decades, a variety of analytical approaches—including spectrophotometry, chromatography (TLC, HPLC, UPLC, GC), hyphenated techniques (LC-MS/MS, GC-MS), electrochemical methods, and capillary electrophoresis—have been developed for their individual and simultaneous quantification in pharmaceutical formulations and biological matrices. Among these, RP-HPLC and LC-MS/MS remain the most widely adopted, offering stability-indicating capability and ultra-sensitive detection, respectively. Method validation in line with ICH Q2(R1) ensures analytical reliability, covering accuracy, precision, linearity, specificity, and robustness. Emerging trends in green analytical chemistry, high-throughput analytical systems, and miniaturized lab-on-a-chip platforms are reshaping the field, focusing on sustainability, efficiency, and regulatory adaptability. This review provides a comprehensive overview of analytical strategies for DXM and MEM, highlighting their clinical importance, methodological challenges, and future perspectives in advanced pharmaceutical and bioanalytical sciences.