Chromatography Forum

I have come across a few methods, mostly older EP or USP, which use sodium perchlorate or perchloric acid in the mobile phase normally in addition to a buffer. While I generally would never consider using these compounds in mobile phase preparation due to the health issues I was wondering what there role in the separation was. I assume that they must be ion pairing agents but wanted to confirm this. Can anyone help?

Thanks
John

A few years ago, my reaction to these compounds was exactly like yours... Why would anyone consider using this?

In the meantime, I have learned a few things. If you want to look at the fundamentals, look at publications in J. Chromatogr. by Yuri Kazakevich and Rosario LoBrutto.

I have first learned from practical application chemists in Germany that the perchlorate ion is useful to manipulate the selectivity of a separation. You may look at it as a very mild ion-pair reagent.

The distribution of perchloric and its salt is very restricted in my country due to terrorist issue. I've got difficulty when try to search determination method for ramipril tablets. Each method used sodium perchlorate in order to get sufficient retention of its impurities. Because I could not get sodium perchlorate I must modify the method. Without perchlorate, in identical pH and percentage of organic solvent we try the method. The impurities are unretained but the main substance still has retention time as far as written in the pharmacopoeia. In this case, we could not perform related substance assay but assay for the tablets still could be done.
We will get trouble when perchlorate is used to retain main substance..

Best regards,
Siswanto Tanuatmojo

Thanks Ewe and syx for your reply.

I believe these are the two articles that Ewe mentioned:

Influence of inorganic mobile phase additives on the retention, efficiency and peak symmetry of protonated basic compounds in reversed-phase liquid chromatography, Journal of Chromatography A, Volume 1049, Issues 1-2, 17 September 2004, Pages 63-73
Li Pan, Rosario LoBrutto, Yuri V. Kazakevich and Richard Thompson

Effect of the counter-anion type and concentration on the liquid chromatography retention of β-blockers, Journal of Chromatography A, Volume 964, Issues 1-2, 26 July 2002, Pages 179-187
Alan Jones, Rosario LoBrutto and Yuri Kazakevich

This brings me to another question, Does anybody have a good substitute that is LC-MS compatible?

Thanks
John

John,

I might want to consider mixed mode columns for retention of your basic compounds with LC/MS compatible mobile phase (TFA, formic acid, ammonium formate and acetate). We did few studies on the effect of buffer nature on retention of charged analytes. Here are topics from our website (http://hplcmethods.com/Applications_By_ ... onName.php)


Effect of Acid on Xantines Separation.
Effect of Buffer Concentration on Resolution of Neutral Compounds (Prednisolone and D-Glucose Pentaacetate).
Effect of Buffer and Chemistry of Column Stationary Phase on Resolution of Neutral Compounds.
Effect of Concentration of Organic Modifier on Retention of Cation and Anions.
Effect of pH on Retention of Basic Compounds on Primesep C Columns.

Also check newsletter devoted to this issue:

http://allsep.com/brochures/SielcNewsletter_0804.pdf

You can go and see how compounds are retained and how you can use different buffers to adjust your selectivity:

http://allsep.com/Technology_NovelStationaryPhases.php

Contact us if you have questions,

regards,

VO


P.S. Disclosure: I am associated with this column manufacturing company

John,

I send you my response, may be it went to your Bulk folder.

Vlad

John,

While it's certainly not identical to perchlorate (especially in terms of UV transparency), TFA is a reasonable candidate to substitute for perchlorate.