Ion Pairing

[JA]

could anyone please suggest useful references, or explain the change in retention mechanism when ion pairing a basic analyte with a TFA mobile phase?

we observed changing RT and elution order for an impure methyl ether-substited pyridine (NMR indicates imp is positional isomer) when reversed phase chromatographing with 0.1% HCOOH in H2O/ACN then 0.1% TFA.

1) H2O/ACN/0.1% HCOOH. prod 6.0 min, imp 7.0 min
2) H2O/ACN/0.1% TFA. imp 12.5 min, prod 13.0 min

does TFA travel down the column paired with the analyte or equilibrate with the stationary phase?

what is it about TFA which makes it suitable for selectivity changes via ion pairing? is it strong acids which will form ion pairs with basic analytes but ion pairs of other strong acid salts (HCl, HBr etc) dont change RT as the anion isn't retained and this is what makes TFA unique?

[Kostas Petritis]

JA,

Such changes in selectivity are very common when you are using weaker to stronger ion-pairing reagents.

Your question remind me of Patthy article where he explains the selectivity differences between TFA and HFBA (see: EXPLANATION OF THE SELECTIVITY DIFFERENCES BETWEEN REVERSED-PHASE ION-PAIR CHROMATOGRAPHIC SYSTEMS CONTAINING TRIFLUOROACETATE OR HEPTAFLUOROBUTYRATE AS PAIRING ION
Author(s): PATTHY M
Source: JOURNAL OF CHROMATOGRAPHY A 660 (1-2): 17-23 FEB 4 1994

In general stronger acids with long alkyl chains are the strongest ion-pairing reagents. I would say SDS and PDFOA are very strong ion-pairing reagents, HFBA and NFPA are in the middle, TFA ion-pairing capability starts to be limited and then anything else (formic, acetic or inorganic salts) I consider them very weak (if at all ion-pairing reagents...).

In your example, if you have used 0.1% HFBA you would have notice the same elution order as with TFA with the difference that resolution between your product and impurity would be even higher.

If you are interested for more references in ion-pairing I would recommend you:

The old articles from Schill and Bidlingmeyer (end of 70's beginning of 80's), then the articles from Bartha and Vigh in middle 80's (they have several articles named: Studies in reversed-phase ion-pair chromatography, I, II, III....etc., and more recently I like the electrical double-Layer model fro ion-pair chromatographic retention on C18 by Liu and Cantwell (Anal Chem. 1991, 63, 2032.).

I guess you can find part of the above in the Snyder et al. book Practical HPLC method development...

Hope the above helps,

Kostas

[JA]

thankyou Kostas.

currently trying to find access to the JChromA article