Evolving Analytical Methods for the Quantification of Methocarbamol: A Critical Review

Methocarbamol (MT), a centrally acting muscle relaxant, presents significant analytical challenges due to its low ultraviolet (UV) absorptivity, rapid metabolism, and pronounced pH-dependent instability. The presence of guaifenesin-related impurities and interference from co-formulated analgesics further complicate its detection in pharmaceutical, biological, and environmental matrices. This review compiles peer-reviewed English-language studies indexed in Scopus, Web of Science, PubMed, ScienceDirect, and Google Scholar and provides a critical assessment of MT quantification methods developed over the past 25 years. Evidence shows that optimized high-performance liquid chromatography (HPLC), particularly fluorescence-based systems, provides the highest sensitivity and selectivity, achieving sub-ng/mL detection and overcoming limitations of UV assays, such as signal suppression and narrow linear ranges. Electrochemical approaches using CNT-, graphene-, MOF-, and magnetic-nanocomposite-modified electrodes enhance redox discrimination and enable nM-μM detection. Chemometric-assisted spectroscopic techniques offer rapid, low-cost analysis suitable for simple formulations but lack reliability in complex matrices. Across all platforms, strict pH control, rapid processing, and selective extraction methods-such as solid-phase extraction (SPE), molecularly imprinted polymer (MIP), and dispersive liquid-liquid microextraction (DLLME) remain essential to reduce degradation and matrix interference. Future progress will rely on miniaturized microfluidic systems, improved stability-indicating chromatography, and intelligent electrochemical sensors capable of multiplex quantification in challenging samples.