Abstract

ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR DEXTROMETHORPHAN: A REVIEW OF CHROMATOGRAPHIC AND SPECTROPHOTOMETRIC APPROACHES

Vinothkumar S., Kamalesh S., Mohanrao A., Arunkumar S., Sriragavan C.K., T. Janarthanan*

ABSTRACT

Dextromethorphan (DXM) has held a place in over-the-counter cough and cold formulations since the late 1950s, valued for its antitussive activity as a non-opioid NMDA receptor antagonist. Despite its long history of therapeutic use, the drug presents a set of analytical challenges that have kept it a subject of active method-development research: it is almost always sold alongside other actives such as antihistamines, decongestants, and expectorants; it carries a chiral impurity, Levo methorphan, that is pharmacologically and legally distinct from DXM itself; and its growing pattern of recreational misuse among adolescents has added a forensic and toxicological dimension to what was once a purely pharmaceutical quality-control problem. This review draws together the major analytical strategies used to identify and quantify dextromethorphan, focusing on reversed-phase HPLC and UV spectrophotometry as the two dominant platforms, while also considering how these methods are validated against ICH Q2(R2) parameters like specificity, linearity, accuracy, precision, and robustness. Particular attention is given to stability-indicating methods capable of distinguishing intact drug from its degradation products, and to the more recent push toward greener, Quality-by-Design-driven method development that weighs environmental impact alongside analytical performance. Taken together, the literature suggests that future work on DXM will need to move past single-purpose assay validation and toward integrated methods that can simultaneously resolve complex multi-drug matrices, control enantiomeric impurities, and meet sustainability benchmarks, reflecting broader shifts in how pharmaceutical analysis is practiced.

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