Study by Shimadzu Scientists Explores On-Line SFE-SFC for Solid-State Extraction and Purification
A new study led by Quentin Gros, a project leader at Shimadzu Corporation, developed a new method for better streamlining supercritical fluid extraction–supercritical fluid chromatography (SFE–SFC) for solid-state injection and purification. Their findings were published in the Journal of Chromatography Open (1).
Long Beach, California, USA - July 10, 2022: Shimadzu Precision Instruments office building in Long Beach, California, USA. Shimadzu Corporation is a Japanese public KK company. | Image Credit: © JHVEPhoto - stock.adobe.com
Supercritical fluids (SCFs) have gradually expanded due to more robust and user-friendly systems. These materials, which are used in states above the critical temperature and pressure where gases and liquids can coexist, have proven useful (2). However, despite being referred to as either, typically during this process, the extraction fluid or the mobile phase are in a subcritical state.
Properties of sub/supercritical fluids benefit from low viscosity and high diffusivity, allowing high flow rate for improved throughput. Among these fluids, carbon dioxide has emerged as a convenient solution for SFE and SFC applications. In a continuous search for creating better, quicker, and automated methods, on-line systems are attractive solutions, with on-line SFE–SFC being a promising candidate. Both parts of these systems benefit from the advantages using sub/supercritical CO2, and their coupling is facilitated since SFE and SFC share similar phase composition(mainly pressurized CO2). However, designing an on-line system can be complicated. It is crucial to select a column based on its chromatographic performance and its trapping efficiency. As such, alternative approaches could be employed to simplify transfers from SFE to SFC.
This study examines the possible benefits of using semi-preparative scale on-line SFE–SFC for solid-state injection and simplifying sample pretreatment before purification. The scientists hoped to examine the possibilities offered by this approach while determining the key parameters for further method development, using ibuprofen as a case study. First, the solubility changes of ibuprofen in a pressurized carbon dioxide (CO2)/methanol mixture were investigated. Next, an SFC method was developed at an analytical scale, then scaled up to semi-prep SFC. Afterwards, the effects of the co-solvent ratio and extraction duration on semi-prep. on-line SFE-SFC solid-state injection were investigated. Finally, the methodology was applied to 2.5 g of sample, demonstrating its suitability for larger solid-state injection.
When the solubility charges were investigated, this revealed a favorable solubility at 20% of the co-solvent. The developed and scaled-up SFE method being combined with semi-prep. SFC allowed for ibuprofen to be properly separated from structurally related compounds in less than 3 min, using a Shim-pack UC PolyVP column and 30% of MeOH in pressurized CO2. Overall, the procedures confirmed the potential of using solid-state injection for semi-prep. purification. Using an extraction oven as a solid autosampler proved interesting and can potentially be effective for samples that are challenging to solubilize and for swiftly loading a sample to facilitate rapid analysis.
Some parameters must be optimized to obtain satisfactory results, one critical example being the choice of the column. A column having poor retentivity strength may yield peak distortion, which is a global challenge for both analytical and semi-preparative online SFE–SFC. However, based off the results, it can also affect solid-state injection sample loading. With poor trapping efficiency, the co-solvent ratio and the duration of the extraction/solid-state injection step might need reduction.
Adjusting co-solvent ratio during static extraction is important for maximizing solubilization and increasing solid-state injection loading capacity without affecting peak shape. Dynamic extraction (DE), which refers to the modern, high-speed, high-capacity, preparative-scale development of countercurrent chromatography (CCC), was essential for maximizing the efficiency of solid-state injection whereas the increase of solid extraction (SE) showed positive but limited effect on sample loading (3). Only increasing DE duration by a few minutes allowed a significant increase of solid-state injection loadability. Overall, the solid-state injection method could prove a cost- and space-saving alternative for existing SFC semi-prep. methods, while having potential applications like racemate mixture purification and drugs deformulation.
References
(1) Gros, Q.; Masuda, Y.; Watabe, Y.; Terada, H. Semi-Preparative On-Line Supercritical Fluid Extraction-Supercritical Fluid Chromatography for Solid-State Injection and Purification. J. Chromatogr. Open 2025, 7, 100206. DOI: 10.1016/j.jcoa.2025.100206
(2) Supercritical Fluid. ScienceDirect 2017. https://www.sciencedirect.com/topics/engineering/supercritical-fluid (accessed 2025-4-17)
(3) Sutherland, I. A.; Garrard, I. J.; Fisher, D. Dynamic Extraction: A High-Speed, High-Capacity Purification Process That is Rapidly Scalable. LCGC N. Am. 2008, 26 (5), 424–438. http://chromatographyonline.com/view/dynamic-extraction-high-speed-high-capacity-purification-process-rapidly-scalable (accesed 2025-4-18)
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