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How to wash away acid from ZIC-pHILIC

Posted: Thu Aug 23, 2007 1:13 am
by plusik
Hello,

we are using ZIC-pHILIC column with ACN as A solution, 10mM ammonium carbonate (pH ~9) as B solution. FTMS is used as detector.

After many injections of cellular extracts, the column got contaminated with Mg salts (MS data show Mg adducts). I tried to use 0.1% formic acid to wash away the Mg. It was successful, but now the column gives very bad peak shapes, especially for polar compounds. I suppose some acid may remain in the column. I tried to flow 100mM ammonium carbonate overnight, but it didn't help. How can I restore the column condition?

Thank you for any advice!

Tomas

Posted: Thu Aug 23, 2007 8:11 am
by k66
Column cleaning: Those of you who read this column regularly know that I am a strong proponent of considering the LC column as a consumable item. Generally, columns will last for 500–1000 injections or more. At this point, the cost of the column amounts to just a few per cent of the total cost of analysis (amortized instrumentation, solvent purchase and disposal, sample preparation, labour and so forth). In such instances, any efforts to restore a failed column, other than a simple solvent flush, are not usually cost effective. However, in the present case, a 50-injection column lifetime is too short and justifies some time spent trying to solve the problem.

A generic column-cleaning procedure for reversed-phase columns is to wash with successive 50 mL aliquots of aqueous mobile phase, then 100% acetonitrile. If this is unsuccessful, an additional wash with methylene chloride can be helpful to remove very hydrophobic materials. Be sure to wash back through acetonitrile to remove all the methylene chloride before using an aqueous mobile phase again. If you know of specific solvents that will solubilize your sample components, there is no harm in trying them — just remember to use solvents in any sequence such that each solvent is fully soluble in the prior one.

As a general rule, today's silica-based reversed-phase columns can tolerate a mobile phase pH of 2–8. For short-term exposure, mobile phase pH outside these limits can be used (I remember trying to damage a column intentionally once by washing with 10 mL of near saturated sodium hydroxide — it had no deleterious effect). Often a low- or high-pH wash will help remove components strongly bound to the column.

There is another recipe that I recommend for removing ion-pairing reagents from the column. This is a 100 mL wash with 200 mM phosphate buffer, pH 6, mixed 50:50 with methanol. The high salt, intermediate organic combination seems to be especially effective at removing ion pairing reagents. However, if you use this, be very careful to avoid conditions that might precipitate the buffer. Wash the column with 50:50 methanol–water before and after treatment. I suspected that this recipe might be useful in the present instance, because the acidic polymers can adsorb to the column in a similar manner to ion pairing reagents, leaving the acid group exposed for ion pairing with the amine analyte. In the present situation, I suggested to try several different solvents first to wash the column. As far as I know, you can't hurt a column by washing it with solvents, so pick the solvent that is most likely to dissolve the polymer. If this is not effective, the next step would be to try a strongly acidic mobile phase, such as 0.2% trifluoroacetic acid in tetrahydrofuran or 0.1 M sodium hydroxide in tetrahydrofuran. If there are any doubts about solubility of washing solutions, test miscibility in a test tube first. Finally, if these do not work, try the ion-pairing flush. The nice thing about the present problem is that the columns are ruined already, so there is no danger of further damaging them by experimental washing procedures. Just be sure to disconnect the detector before flushing so that nothing is washed into the detector inadvertently.

This situation reminds me of a method I used to analyse a basic drug in a tablet formulation. The method required an extraction procedure to remove interferences. The tablet was dissolved in a high pH aqueous solvent, which converted the drug to its non-ionized form. This solution was extracted with methyl-t-butyl ether, so the drug partitioned into the organic solvent, leaving aqueous-soluble interferences behind. However, a polymer in the formulation also extracted into the organic phase, so a back extraction was performed by shaking the sample with 0.1 N hydrochloric acid and the now-ionized form of the drug partitioned into the aqueous phase, leaving the polymer in the organic. A similar clean-up process might apply in the present situation to help remove residual polymer from the sample before injection. A lower polymer load in the injected sample should extend column life.

The results: The reader first tried flushing with a combination of methylene chloride and 0.2% trifluoroacetic acid. This appeared to remove some of the contaminant, as evidenced by a return of approximately half the response of the amine. Next, a mixture of 0.2% trifluoroacetic acid in toluene was tried and 100% of the amine response was recovered. It is clear that a few hours trying various wash procedures was well worth the effort. Now a routine flushing with the 0.2% trifluoroacetic acid–toluene wash solvent can be incorporated in the method at the end of each batch of samples.

FROM: http://www.lcgceurope.com/lcgceurope/ar ... =&pageID=4

perhaps something help You in your situatin :)

Posted: Fri Aug 24, 2007 11:15 pm
by Kostas Petritis
The article that was copied/pasted by k66 refers to reversed phase material that do not apply in your case. In the case of Mg salts, I would try to wash them out with an aqueous solution of high salt concentration. You choose to do it with formic acid that a priori shouldn't hurt this type of columns.

At this point, I would go with the manufacturer recommendation: wash the column with 100% water first, then flush with 0.5 M sodium chloride solution, then again with 100% water and then back to your initial conditions. If that does not work, it is maybe time for a new column.

How many injections does your column have already?

Posted: Mon Aug 27, 2007 2:06 am
by plusik
Thank you for all comments.
First I tried to wash using 100mM salt, but it didn't help, that's why I tried the acid.
After trying to wash away the acid with water for the whole weekend, the conditions got a little better, but still far from perfect. Finally I decided to change the column, cause I need to continue with sample analysis...
Now the conditions are OK.
If I have problems with Mg contamination again, I will try 500mM salt first.