Comprehensive multidimensional liquid chromatography for advancing environmental and natural products research

Chromatography is the separation method of choice in most laboratories worldwide. Nonetheless, the increasing need to decode complex samples has created a demand for better separation skills. The addition of extra separation dimensions to a conventional liquid chromatography system was one of the ways to answer to this demand. Although very common in proteomics and polymer research, the use of Multidimensional Liquid Chromatography (MDLC) coupled to high-resolution detectors for separation and analysis of environmental and natural products samples has yet to receive the deserved attention. This article presents a critical review on the most prominent of these comprehensive MDLC methods for targeted and untargeted analysis of complex environmental and natural products samples. This article also discusses the practical aspects of applying peak capacity and orthogonality concepts in MDLC analysis of complex matrices. It also addresses the limitations and challenges ahead for advancing environmental and natural products research using comprehensive MDLC.Thanks are due to FCT/MCTES for the financial support to CESAM (UID/AMB/50017/2019) and project AMBIEnCE (PTDC/CTA-AMB/28582/2017), through national funds (OE). FCT/MEC and the European Social Fund are also acknowledged for a PhD grant (PD/BD/142931/2018) and an Investigator FCT Contract (IF/00798/2015).publishe