November 1st 2018Supercritical fluid chromatography (SFC) and hydrophilic interaction liquid chromatography (HILIC) are suitable for screening very polar trace organic compounds in environmental water samples. The polarity range of separable compounds in SFC is as broad as the polarity range of the serial coupling of reversed‑phase liquid chromatography and HILIC (reversed-phase LC–HILIC). In this article the orthogonality of SFC and reversed-phase LC–HILIC is assessed. It is shown that both techniques are highly orthogonal and complementary. The parallel use of the two techniques offers additional benefits for the compound monitoring of, for example, pharmaceuticals in surface waters, or the identification of unknown compounds in complex samples.