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Intact non-covalent biological complexes resulting from interactions in solutions have been observed by matrix-assisted laser desorption\u002Fionization time-of-flight mass spectrometry (MALDI TOF-MS). However, their analysis is hampered by the presence of non-specific, non-covalent complexes (clusters) produced under MALDI conditions. A study of the influence of laser energy and ion extraction conditions allows information to be obtained on (i) the collision regime in the plume and (ii) ion stability, through the abundances and time-of-flight ( t\u003Cjats:sub>tof\u003C\u002Fjats:sub>) deviations of bovine insulin clusters using a sinapinic acid matrix. In the linear mode, it is shown that (i) the neutral contribution to quasi-molecular peaks is below 10% and (ii) for related cluster species, the t\u003Cjats:sub>tof\u003C\u002Fjats:sub> difference between neutrals and ions is less than 10 ns. Although the abundance of cluster ions increases relatively to the abundance of the monomeric ions with laser energy, heavier cluster ions are unfavored at higher laser energy. 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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\u002For 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\u002FMS is performed with atmospheric pressure ionization (API) sources. Unlike LC\u002FMS, 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\u002FMS using these various interfaces are also discussed. \u003C\u002Fjats:p>",{"EN":475},"Advantages and Drawbacks of Popular Supercritical Fluid Chromatography \u002F Mass Spectrometry Interfacing Approaches—A User's Perspective",{"VOID":477},"16046803",{"VOID":479},"10.1255\u002Fejms.731",[146],"https:\u002F\u002Fjournals.sagepub.com\u002Fdoi\u002F10.1255\u002Fejms.731",[483],{"id":484,"sortIndex":25,"researcher":24,"roles":485,"affiliations":486,"properties":497},"6237048f-e014-4394-8e23-c0bb922c3f36",[],[487],{"id":488,"sortIndex":25,"affiliation":489,"properties":24},"724ccd5a-2d48-4ae2-94fc-af9968d40c7c",{"id":490,"createTime":491,"updateTime":491,"relativeEntities":492,"slug":493,"properties":494,"entityType":61,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"3844fa90-b097-4cb9-9a74-f2b7a2728a61","2024-10-08T01:14:05.839+00:00",[],"Procter-Gamble-Pharmaceuticals-Health-Care-Research-Center-8700-Mason-Montgomery-Rd-PO-Box-8006-Mason-OH-45040-USA",{"title":495},{"EN":496},"Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Rd, PO Box 8006, Mason, OH 45040, USA",{"openalex":498,"title":500},{"VOID":499},"A5037817684",{"EN":501},"J. 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