Recent Advances in LC–MS-Based Pharmaceutical Analysis: Emerging Technologies, Applications, and Future Perspectives

Abstract

Liquid chromatography–mass spectrometry (LC–MS) has become one of the most powerful analytical platforms in modern pharmaceutical analysis. This systematic review critically evaluates advances reported between January 2020 and December 2025 in chromatographic separation, high-resolution mass spectrometry, sample preparation, artificial intelligence, and green analytical chemistry. A structured literature search was conducted in Scopus, Web of Science, PubMed/MEDLINE, ScienceDirect, SpringerLink, Wiley Online Library, and Google Scholar, with supplementary reference-list screening. Eligible peer-reviewed studies were qualitatively synthesized in accordance with PRISMA 2020. The reviewed evidence indicates that UHPLC–HRMS platforms, particularly Orbitrap and Q-TOF systems, have improved sensitivity, selectivity, mass accuracy, throughput, and confidence in structural elucidation. Miniaturized extraction and solvent-saving procedures have strengthened analytical efficiency and environmental sustainability, while artificial intelligence and machine-learning tools have accelerated peak detection, feature alignment, spectral interpretation, and decision support. Major applications include drug discovery, bioanalysis, impurity profiling, metabolite identification, stability testing, and pharmaceutical quality control. Nevertheless, routine implementation remains constrained by high acquisition and maintenance costs, data complexity, limited workflow standardization, regulatory validation requirements, and the need for specialized analysts. Future progress will depend on interoperable digital platforms, harmonized validation frameworks, greener sample preparation, and multidisciplinary training and research.