Metabolism and bioavailability aspects of natural products of plant origin using mass spectrometry-based and metabolomic approaches

models have been developed to study the ADME properties of xenobiotics, while human clinical trials remain scarce in the field of NPs. Recent technological advancements, including innovations in mass spectrometry (MS), smart library screening, dereplication, molecular networking, and metabolomics, have significantly improved the NP research pipeline, offering faster and more accurate compound identification. High-resolution instruments like Orbitrap, QTOF, FT-ICR, and MRMS, alongside IMS and advanced data acquisition techniques (DDA and DIA), now offer deeper insights into complex mixtures. Despite MS being a cornerstone of pharmacokinetics-pharmacodynamics (PK/PD) studies, the integration of metabolomics and big data analytics remains underutilized, particularly in NP prioritization. This review aims to explore the evolution of MS in NP metabolism studies, from early investigations to current multidisciplinary approaches, proposing a critical reflection on the challenges in NP drug development.