Bridging the gap between gas and liquid chromatography

•Low-density carbon dioxide enables retention of volatile compounds.•The column efficiency is maximized by complete thermal insulation (P < 10−4 Torr).•Volatile and non-volatile compounds can be separated in a single SFC run.•The method is applied to volatile terpenes in Marijuana plant extracts.

The rapid and complete baseline separation of both volatile (C5 to C16 alkanes in gasoline or terpenes in plant extracts) and non-volatile (>C20 alkanes) organic compounds was achieved by combining (1) low-density fluid chromatography (LDFC) using carbon dioxide at elevated temperature (>90 °C) and low pressure (1500 psi) designed to increase the retention of the most volatile compounds and (2) high-vacuum technology (<10−4 Torr) in order to preserve the maximum efficiency of short analytical columns (3.0 mm × 150 mm packed with 1.8 μm fully porous HSS-SB-C18 particles) when used in LDFC. The volatile compounds are eluted first under isobaric conditions (1500 psi) in less than a minute followed by a linear gradient of the column back pressure (from 1500 to 3500 psi in 5 min) for the elution of the non-volatile compounds up to C40. The experimental results demonstrate that LDFC performed with short 3.0 mm i.d. columns packed with sub-2 μm particles and placed under adiabatic conditions enables the analysts to deliver a single, fast, and high-resolution separation of both volatile and non-volatile compounds.