Phosphopeptides, organic acids or nucleotides are acidic and can gain a negative charge in the liquid phase. When it comes to LCMS analysis this charge introduces a second dimension of selectivity and causes tailing in HILIC chromatography, especially in presence of positively charged metal ions (low purity silica).
Formly chelating properties of EDTA have been used to remove most metal ions but this additive caused ion supression in downstream ESI ionization. To overcome this incompartibility with ESI MS analysis the use of medronic acid was investigated. As it turns out medronic acid has a much higher affinity for metal ions than phosphopeptides and phosphorylated compounds and displaying much less ion supression compared to EDTA in ESI MS.
https://pubs.acs.org/doi/10.1021/acs.analchem.8b02100
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