SEC-MALLS AND HYPHENATED ANALYTICAL TECHNIQUES IN PHARMACEUTICAL CHARACTERISATION: APPLICATIONS IN MOLECULAR WEIGHT AND STRUCTURAL ANALYSIS
DOI:
https://doi.org/10.22376/ijlpr.v16i1.2036Keywords:
SEC-MALLS, Hyphenated analytical techniques, Molecular weight determination, Biopharmaceutical characterisation, Nanomedicine analysis, Structural characterization, multi-angle light scatteringAbstract
Size Exclusion Chromatography coupled with Multi-Angle Laser Light Scattering (SEC-MALLS) and hyphenated analytical techniques have emerged as powerful analytical platforms for molecular weight determination and structural characterization of pharmaceutical and biopharmaceutical products. The increasing complexity of biologics, biosimilars, proteins, peptides, vaccines, polymers, and nanomedicine formulations has created significant demand for advanced analytical methodologies capable of simultaneous molecular separation, aggregation profiling, and structural analysis. SEC-MALLS combines chromatographic separation based on hydrodynamic volume with absolute molecular weight determination through multi-angle light scattering detection, thereby enabling comprehensive characterisation of molecular mass, size distribution, aggregation behaviour, conformational stability, and molecular heterogeneity without dependence on calibration standards. In addition to SEC-MALLS, several hyphenated analytical systems, including LC-MS, LC-MS/MS, LC-NMR, GC-MS, CE-MS, SEC-DLS, SEC-RI, and SEC-UV, provide enhanced analytical sensitivity, structural elucidation capability, and impurity profiling for complex pharmaceutical systems. The present review comprehensively discusses the principles, instrumentation, working mechanisms, applications, method development strategies, analytical advantages, and limitations of SEC-MALLS and multidetector hyphenated analytical techniques in pharmaceutical characterisation. Particular emphasis is placed on applications in monoclonal antibody aggregation studies, protein characterisation, biosimilar comparability assessment, nanoparticle analysis, liposomal formulations, dendrimers, and advanced drug delivery systems.
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