In the field of petroleomics and metallopetroleomics, the gel permeation chromatography (GPC) technique coupled with high-resolution detection technologies has made significant contributions as an analytical and preparative tool for over five decades. This bibliographic minireview highlights the study of the supramolecular and structural behavior of heavy crude oil and its fractions, as well as their reactivity to various processes by use of GPC. The preferred mobile phase is tetrahydrofuran (THF), whereas the stationary phase is polystyrene–divinylbenzene copolymer to avoid compound retention in the column. Other techniques such as HPTLC, RPLC, and NPHPLC have been used to provide multidimensional separations complementary to GPC. The high molecular weight (HMW) fraction, due to its greater polarity, reactivity to polymerization, and resistance to hydrodemetallization processes, has been the focus of interest for years. GPC coupled with high-resolution techniques has proven to be reliable for the detection of organic and inorganic species in bio-oils, making it a valuable tool for researchers and industry professionals in the context of feedstocks changes and new energy production.
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