Hyphenation of packed column supercritical fluid chromatography with mass spectrometry: where are we and what are the re

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Hyphenation of packed column supercritical fluid chromatography with mass spectrometry: where are we and what are the remaining challenges? Laura Akbal 1 & Gérard Hopfgartner 1 Received: 14 April 2020 / Revised: 7 May 2020 / Accepted: 14 May 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Over the last decades, packed column supercritical fluid chromatography (pSFC) using carbon dioxide (CO2) as supercritical fluid has gained interest as a complementary separation technique to liquid chromatography (LC). Various commercial solutions for the hyphenation to atmospheric pressure ionization (API) including electrospray (ESI) and atmospheric pressure chemical ionization (APCI) have been described using split-flow or full-flow introduction approaches. This review discusses various aspects of the hyphenation using these two approaches. It also illustrates the difference between LC-MS and SFC-MS. The benefits and challenges of the decoupling of the separation mobile phase from the ionization conditions are also pointed out. The effect of CO2 on ESI performance and the adduct reduction are also discussed. Finally, limitation of current hardware and the limited use of smaller column internal diameters (i.d.) are discussed. Keywords Supercritical fluid chromatography . Mass spectrometry . Electrospray . Ionization . Hyphenation . Review

Introduction Supercritical fluid chromatography (SFC) using either packed columns (pSFC) or open tubular capillary columns (cSFC) has experienced ups and downs since its first introduction in 1962 [1]. SFC has mainly survived for its performance in enantiomeric separation and a renaissance is observed since 2010 with the commercialization of improved hardware for pSFC [2]. Carbon dioxide (CO2) is applied in most cases as the mobile phase, because its critical parameters (critical temperature T = 31 °C and critical pressure P = 73 bar) are easily reachable. Moreover, it is cheap, non-toxic, and non-inflammable. In SFC, the mobile phase is delivered by regular high-pressure piston or syringe pumps equipped with a cooling system. The supercritical conditions are generally maintained, post-column, by a capillary restrictor in the case of cSFC or a back pressure regulator (BPR) for pSFC. Until the 1990s, SFC was mostly applied as an extension of gas chromatography (GC) [3] with flame ionization detection or mass spectrometry detection [4]. * Gérard Hopfgartner [email protected] 1

Life Sciences Mass Spectrometry, University of Geneva, 24 Quai Ernest Ansermet, 1211 Geneva 4, Switzerland

Since that time, cSFC has lost interest and pSFC, using common HPLC packing materials and UV, evaporative light scattering detector (ELSD), and mass spectrometry (MS) took over for most applications. Nowadays, pSFC is seen as a hybrid green separation technique of GC and LC with high separation efficiency and short analysis time. Supercritical CO2 has a polarity close to that of hexane and it is well suited for the analysis of lipids or polar compounds with the use of a