Designs and methods for interfacing SFC with MS.

Hyphenating SFC with MS is now routinely performed in analytical laboratories. Major instrument providers supply commercial solutions for coupling SFC and MS, which has facilitated wider adoption of the technology. The current status, however, could be achieved based on the work done by many researchers over decades. Interfacing SFC with MS posed some unique challenges, compared to interfacing MS with LC or GC, demanding special solutions. Several interface designs were tried and tested over the years before suitable solutions could be detected. Additional measures, such as (a) mixing SFC mobile-phase with an additional liquid solvent at the column outlet, and (b) heating the interfacing device, had to be adopted to address some specific challenges. Although such modifications and measures look diverse, there is one factor that drove most of them - compressibility of SFC mobile-phase. There are two objectives of this review - (1) to compile various insights which were reported on describing and optimizing SFC-MS interfacing processes, and (2) to link these insights with the fundamental issue of solvent compressibility.