Chaotropic additives counteranions

It has been shown that the PFe counteranion has had the greatest effect on the improvement of the peak asymmetry at low concentrations compared to other chaotropic additives. At the highest concentration of counteranions (PFe , CIO4, BF4), the number of plates for most of the basic compounds studied was similar to that of the neutral markers. In contrast, the neutral... 

The chaotropic effect is dependent on the concentration of the free counteranion and not the concentration of the protons in solution at pH < basic analyte Ka. This suggests that change in retention of the protonated basic analyte may be observed with the increase in concentration of the counteranion by the addition of a salt at a constant pH as shown in Figure 4-47 for a pharmaceutical compound containing an aromatic amine with a pKa of 5. 

The analysis of Dorzolamide HCl at pH 2 with phosphoric acid shows early elution. The addition of hexafluorophosphate to the mobile phase leads to an enhancement of the retention. Figure 4-59 is an overlay of Dorzolamide HCl chromatograms at four increasing PFe concentrations. As the concentration increased, peak tailing decreased, and peak efficiency and analyte retention increased. Figure 4-60 shows the effect of different counteranions on basic analyte retention and peak efficiency. Depending upon the desired selectivity between a neutral component and a charged basic analyte, a particular chaotropic counteranion could be employed. 

The use of chaotropic counteranions for a chromatographic separation is beneficial as a method development strategy. These modiflers may replace the need for changing column type and/or addition of hydrophobic ion-pairing reagents for the more challenging separations. Further studies are needed to fully elucidate the detailed mechanism of chaotropic mobile-phase additives. 

Yes, you can adjust the pH of the mobile phase by addition of an acid (preferably with low pA ) and then increase counteranion concentration by adding its salt. The retention increase will be solely due to the increase of the chaotropic counteranion. This approach may be needed to fine tune a method. For example, if a mixture of acids and bases is not optimally resolved at a certain pH then the addition of perchlorate anion will increase the retention of only the protonated basic compounds without affecting the retention of the acidic compound or other basic compounds that are not fully protonated at this pH. In order to calculate the total concentration of perchlorate anions present, the concentration of perchlorate anion from the addition of perchloric acid and sodium perchlorate must be known. 

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