Abstract
High-performance liquid chromatography (HPLC) remains an indispensable analytical tool in pharmaceutical, environmental, and biochemical sciences. However, conventional HPLC workflows are increasingly challenged by high solvent consumption, energy demands, and environmental footprints. The paradigm of Green, Portable, and Smart HPLC has emerged as a transformative response aligning analytical chemistry with sustainability and digitalisation goals. The integration of green analytical chemistry (GAC) principles, miniaturised architectures, and artificial intelligence (AI)-driven automation has enabled low-solvent, high-efficiency, and intelligent chromatographic operations. This review comprehensively discusses the transition from traditional solvent-intensive systems to eco-efficient, portable, and digitally integrated chromatographic technologies. It critically examines solvent substitution strategies, environmentally benign stationary phases, micro- and nano-HPLC systems, and AI-enhanced method optimisation. Furthermore, the role of Internet of Things (IoT), cloud analytics, and hybrid HPLC-MS platforms in real-time monitoring and field deployment is explored. The review also analyses current regulatory validation frameworks, economic implications, and the evolving vision toward autonomous, self-learning chromatographic systems. Collectively, these innovations signify a paradigm shift toward sustainable and intelligent HPLC, harmonising analytical excellence with environmental stewardship and operational efficiency.