Advantages and Drawbacks of Popular Supercritical Fluid Chromatography / Mass Spectrometry Interfacing Approaches—A User's Perspective

Mobile phases in supercritical fluid chromatography (SFC) have low viscosities and high diffusion coefficients with respect to those of traditional high-performance liquid chromatography (HPLC). These properties allow higher mobile phase flow rates and/or longer columns in SFC, resulting in rapid analyses and high efficiency separations. In addition, chiral SFC is becoming especially popular. Mass spectrometry (MS) is arguably the most popular “informative” detector for chromatographic separations. Most SFC/MS is performed with atmospheric pressure ionization (API) sources. Unlike LC/MS, the interface between the SFC column and the API source must allow control of the downstream (post-column) pressure while also providing good chromatographic fidelity. Here, we compare and contrast the popular interfacing approaches. Some are simple, such as direct effluent introduction with no active back pressure regulator (BPR) in high-speed bioanalytical applications. The pressure-regulating fluid interface is more versatile and provides excellent chromatographic fidelity, but is less user friendly. The pre-BPR-split interface and an interface which provides total flow introduction with a mechanical BPR are good compromises between user friendliness and performance and have become the most popular among practitioners. Applications of SFC/MS using these various interfaces are also discussed.