The widening application area of SFC-MS with polar analytes and water-containing samples facilitates the use of quick and simple sample preparation techniques such as “dilute and shoot” and protein precipitation. This has also introduced new polar interfering components such as alkali metal ions naturally abundant in e.g. blood plasma and urine, which have shown to be retained using screening conditions in SFC/ESI-TOF-MS and causing areas of major ion suppression. Analytes co-eluting with these clusters will have a decreased signal intensity, which might have a major effect on both quantification and identification. When investigating the composition of the alkali metal clusters using accurate mass and isotopic pattern, it could be concluded that they were previously not described in the literature. Using NaCl and KCl standards and different chromatographic conditions, varying e.g. column and modifier, the clusters proved to be formed from the alkali metal ions in combination with the alcohol modifier and make-up solvent. Their compositions were [(XOCH₃)_n + X]⁺, [(XOH)_n + X]⁺, [(X₂CO₃)_n + X]⁺ and [(XOOCOCH₃)_n + X]⁺ for X = Na⁺ or K⁺ in ESI+. In ESI−, the clusters depended more on modifier, with [(XCl)_n + Cl]⁻ and [(XOCH₃)_n + OCH₃]⁻ mainly formed in pure methanol and [(XOOCH)_n + OOCH]⁻ when 20 mM NH₄Fa was added.

To prevent the formation of the clusters by avoiding methanol as modifier might be difficult, as this is a widely used modifier providing good solubility when analyzing polar compounds in SFC. A sample preparation with e.g. LLE would remove the alkali ions, however also introducing a time consuming and discriminating step into the method. Since the alkali metal ions were retained and affected by chromatographic adjustments as e.g. mobile phase modifications, a way to avoid them could therefore be chromatographic tuning, when analyzing samples containing them.

SFC-MS带有极性分析物和含水样品的应用领域不断扩大，这有利于快速，简单的样品制备技术的使用，例如“稀释并射击”和蛋白质沉淀。这也引入了新的极性干扰成分，例如天然存在于血浆和尿液中的碱金属离子，这些碱金属离子在SFC / ESI-TOF-MS中使用筛选条件已被保留，并导致了主要的离子抑制区域。与这些簇共洗脱的分析物信号强度会降低，这可能会对定量和鉴定产生重大影响。当使用精确的质量和同位素模式研究碱金属簇的组成时，可以得出结论，以前没有在文献中对其进行描述。使用NaCl和KCl标准溶液以及不同的色谱条件（例如色谱柱和改性剂），可以证明簇是由碱金属离子与醇改性剂和补充溶剂共同形成的。他们的组成是[（XOCH₃）_Ñ  + X] ⁺，[（XOH）_Ñ  + X] ⁺，[（X ₂ CO ₃）_Ñ  + X] ⁺和[（XOOCOCH ₃）_Ñ  + X] ⁺为X =钠⁺或K ⁺的ESI +。在ESI-中，团簇更多地依赖于改性剂，其中[（XCl）_n  + Cl] ^-和[（XOCH ₃）_n  + OCH ₃ ] ^-主要由纯甲醇形成，而[（XOOCH）_n  + OOCH] ^-在20时形成mM NH ₄Fa被添加了。

通过避免使用甲醇作为改性剂来防止簇的形成可能很困难，因为这是一种广泛使用的改性剂，在分析SFC中的极性化合物时具有良好的溶解性。使用例如LLE的样品前处理将去除碱金属离子，但是，该方法也引入了耗时且费力的步骤。由于碱金属离子被保留并受到色谱调整（例如流动相修饰）的影响，因此，在分析包含碱金属离子的样品时，避免它们的方法可以是色谱调整。