Inductively Coupled Plasma Mass Spectroscopy: A Comprehensive Review of Principles, Instrumentation, Analytical Procedures, and Pharmaceutical Applications

Abstract Inductively coupled plasma mass spectrometry (ICP-MS) has emerged as one of the most powerful analytical techniques for elemental and isotopic determination since its introduction in the 1980s. By coupling a high-temperature argon plasma ionization source with a mass spectrometer, ICP-MS enables rapid, multielement analysis with detection limits at trace and ultratrace levels, often reaching the parts-per-trillion range. This review provides a comprehensive overview of the fundamental principles, instrumentation, and diverse applications of ICP-MS, with emphasis on recent advancements and pharmaceutical relevance. Key components such as plasma generation, ionization mechanisms, sampler–skimmer interface, ion optics, and mass analyzers (quadrupole, sector field, time-of-flight, and multi-collector systems) are critically discussed. Developments in collision/reaction cell technology, tandem ICP-MS, and sample introduction approaches, including nebulization, hydride generation, electrothermal vaporization, and laser ablation, have significantly enhanced accuracy and reduced interferences. Hyphenated techniques, such as HPLC-ICP-MS and CE-ICP-MS, further support speciation studies, expanding the scope of biomedical and pharmaceutical analysis. ICP-MS finds widespread application in clinical diagnostics, environmental monitoring, geochemistry, nanomaterials characterization, and metallomics, enabling high-precision isotope ratio measurements and elemental imaging. Despite its strengths-ultra-trace sensitivity, wide dynamic range, and versatility-ICP-MS faces challenges such as spectral interferences, matrix effects, and high operational costs. Continuous innovations in instrumentation and methodology aim to overcome these limitations, ensuring broader applicability in analytical and pharmaceutical sciences. Overall, ICP-MS remains a versatile, indispensable tool for modern elemental and isotopic analysis, with growing potential in healthcare, materials science, and environmental safety.