Substitution for Sodium Perchlorate in Mobile Phase

[syx]

Dear Chromatographers,

We need help in analytical method for ramipril tablets. In the reference methods we have, sodium perchlorate was used in the mobile phase. This substance is difficult to find in our country. The distribution of sodium perchlorate is restricted by our Police Department due to bomb issue.
If we want a substitution, what are other substances that have same properties and function with sodium perchlorate in the mobile phase?
Every suggestion will be appreciated.

Regards,
SYX

[Steve]

syn

We have developed a method for the seperation of ramipril without sodium perchlorate in the mobil phase. The answer is going to be in the modification of the temperature which you will need to control. Column heater and accurate mobil phase temperature control is needed.


Here is the web site
https://www.macherey-nagel.ch/web/MN-WE ... =HPLC00290

[syx]

Thanks for Steve, ... and another question:
What is the advantage of using perchlorate or perchloric acid compared with other buffers or acids in mobile phase?

[Steve]

It is known that chaotropic ions such as perchlorate, iodide, and thiocyanate disrupt and decrease hydrophobic bonds.

[Chris Pohl]

SYX,

If you are interested in substituting for perchlorate with an alternative polarizable anion (biologists like to refer to polarizable ions as chaotropic ions because polarizable ions are poorly hydrated and therefore disrupt the organized structure of water, thus resulting in a more "chaotic" environment than highly hydrated anions such as chloride or sulfate which are significantly less disruptive of the structure of water), there are a few options which are non-UV absorbing including tetrafluoroborate and hexafluorophosphate. Neither, however, is an exact match for perchlorate with tetrafluoroborate being somewhat less polarizable and hexafluorophosphate being significantly more polarizable than perchlorate. Another alternative would be to substitute species which are marginally functional as "ion pair reagents" such as trifluoroacetic acid (although perhaps a better match would be pentafluoropropionic acid or heptafluorobutyric acid) which are only weakly absorbing in the UV or the analogous short chain sulfonates (propanesulfonic acid or butanesulfonic acid) which do not absorb in the UV.

[syx]

Thanks for the replies.
Mr. Pohl, could you please tell me about the concentration of each compound you have said in the mobile phase?

[Chris Pohl]

syx,

I can't give you the exact concentrations on such substitutions as this is dependent upon the analyte, the ion pair reagent and the solvent system. As a general rule, I would simply start with the same concentration specified in the method for perchlorate. However, if the perchlorate concentration for your method is above the 0.05 M, I would start with 0.05 M as this should be more than sufficient and some of the regents I mentioned might be a bit expensive to use at concentrations higher than this (in fact, you might want to start out with 0.02 M to keep the costs reasonable although this may necessitate some adjustment of the method).

[HW Mueller]

It is usually forgotten that near or below an ionic strength of roughly 0.1 just about all salts have properties which one attributes to chaotropy, even the strongly lyotropic salt Na2SO4. So one can use just about any salt at low concentrations to "deorganize" water (increase entropy.....).

[Chris Pohl]

Hans,

You're quite right that any salt that at high enough concentrations is "chaotropic". This is why I don't really like using that term in conjunction with ion pair reagents or "pseudo ion pair reagents". The driving force behind the action of such reagents has very little to do with whether or not they disrupt the structure of water and much more to do with the solubility "salt" of the analyte and the ion pair reagent in the mobile phase. While this property is certainly correlated to disruption of the water structure, the real reason that perchlorate has an affect on the retention time of a cationic solute is related to the solubility of the salt of these two components relative to the solubility of the analyte with another potential anion. For example, you can be quite certain that the retention time of the perchlorate salt of a cationic solute will always be greater than the retention of the same solute in the presence of the identical concentration of the sulfate. So while sulfate might be useful for disrupting water structure isn't particularly effective at inducing retention of cationic solutes (except, perhaps at substantially higher concentrations).

[HW Mueller]

I was not thinking of perchlorate as ion pair partner, rather my thoughts were going along increasing hydrophobic interaction of analyte with the stationary phase.

I am at a loss, to be honest, regarding practical understanding of this matter of ion pair versus stat phase modification arguments of retention when "ion pairing" agents are invoked.

[tom jupille]

Hans, this may help put things in perspective.

American poet John Godfrey Saxe (1816-1887) based the following poem on a fable which was told in India many years ago.

It was six men of Indostan
To learning much inclined,
Who went to see the Elephant
(Though all of them were blind),
That each by observation
Might satisfy his mind

The First approached the Elephant,
And happening to fall
Against his broad and sturdy side,
At once began to bawl:
“God bless me! but the Elephant
Is very like a wall!â€

[HW Mueller]

Yes! Sort of Plato´s "Allegory of the Cave".

[mross]

Have been using perchloric for many years. I suspect that the mechanism is very different to chaotropism. The solubility of perchlorate in organic phase is very high---therefore it is quite possible that the perchlorate is adsorbed onto the C18 [like soap chromatography] producing an electron rich charged stationary phase. This would also explain why even 1% perchloric acid [very low pH] does not appreciably attack the column and the life of columns under such "extreme" conditions is excellent

[Chris Pohl]

mross,

Actually, if you do the experiment you propose you'll find very little perchlorate actually partitions into the stationary phase. This is the reason that I classify perchlorate as a "pseudo ion pair reagent". And as Tom nicely pointed out above, there are many different opinions on this matter but from my point of view, for something to be a true ion pair reagent it needs to have substantial affinity for the stationary phase in the absence of the analyte and induce electrostatic interactions with analyte. Perchlorate is one of a number of commonly used reagents which have only minimal affinity for hydrophobic surfaces but instead act by substantially reducing the solubility of the analyte in the mobile phase, increasing the partition coefficient toward the stationary phase. Furthermore, if perchlorate were substantially enriched on the stationary phase this would be expected to reduce the stability of the C18 phase as this would create a local pH which was even lower than that of the mobile phase.

[mross]

The solubility of perchloric acid is actually high in organics and if you run a 0.01 M solution through a reverse phase column and monitor the pH you will see that there is an appreciable time before the chlorate ion appears [above dead volume]. Also all perchlorate salts are known to be different to other salts-pparticularly lithium-see link below. The comment about acid stability---it was explained to me a long time ago that the structure of the perchlorate ion is such that the HO-Cl part is what will be in the hydrophobic stationary phase and the negative charges will be clustered on the surface associated with the protons--thus actually the microenvironment near the silica surface is not acid and therefore the column is stable [even in 1% perchloric].

http://www.gfschemicals.com/technicalli ... 100102.asp