Having acceptance problem with PrimeSep column

[vickig]

I developed a lovely method for 7 rather basic impurities on a Primesep 200 HPLC column. My client's response is as follows:

"I noted that you are using a Sielc Technologies PrimeSep 200 column. I am a bit concerned about the use of a specialty column like this (i.e., mixed mode) for a commercial drug product/API release and stability indicating HPLC method. I am not aware of another manufacturer that makes a column equivalent to the PrimeSep 200. Are you? My preference would be to work with a column chemistry/geometry that is supplied by multiple manufacturers."

How do I address this?

[mbicking]

Your client is naive about column chemistry. The fact that you can buy a gazillion C18 columns in the same dimensions and particles sizes means nothing. What matters is whether the separation would be the same, which is to say, is the "selectivity" the same? And across the entire spectrum of C18 columns, the answer is "no."

There are columns that are "similar" and thus could be substituted with little (but not no) change in retention/selectivity, but this is not a perfect science. The USP has two on-line databases that can find similar columns, and there have been multiple threads here about the subject.

Back to your question, ...

Explain the unique nature of this phase and the advantages over traditional phases. What your client may really be worried about is that in 5 years SIELC may go away and then there won't be any way to get the columns. Maybe they could just buy up 10 or 20 now, just to have on hand (bet that would make Vlad happy!).

Or, offer to show, or maybe develop, a comparable method on a phase that is more "traditional" and/or from a major manufacturer. Maybe it won't be as convenient, but it would at least provide a backup option.

[Kostas Petritis]

I partially agree with mbicking, although from the tone of your client message, it looks like that he/she just looks for some reassurance and that he would be OK if you provide a logical explanation (he is "a bit concerned" and not seriously concerned).

About the column chemistry that is supplied by multiple manufacturers he might refer to generic chemistries such as some Kromacil/Hypercil/YMC columns that are offered by different sources?

I think that it would be reassuring to him if you add that in general small companies with succesful column chemistries are ended up being bought by larger companies and give some market examples...

[vickig]

Thank you Kostas and mbicking for your thoughtful and informative replies.

[Vlad Orlovsky]

Hello Vickiq,

I will respond as a manufacturer of Primesep columns and will try to “pleadâ€

[vickig]

Thanks Vlad. I, too, am becoming a big fan of mixed mode columns in general and Primesep columns in particular. The Sielc web site has been most helpful. Kostas also brought up a good point in that small companies with successful column chemistries often up being bought by larger companies.

Tell me one more thing...why the recommendation to limit THF to 10%?

[Vlad Orlovsky]

Vicki,

We have PEEK parts inside the column which seal the column (cap in the drawings
http://www.sielc.com/Column_Hardware_Analytical.html

at higher concentrations PEEK can swell a little and the column might start leaking if you exceed certain pressure (3000 psi) If you look at the drawings you will see what I am talking about. IN some special cases we can pack our material in traditional compression ring columns but we prefer our own hardware which has a lot of benefits

[Mattias]

Vlad> Do you have any plans to manufacture columns with smaller particles than 5 µm?

[Vlad Orlovsky]

Mattias,

We have 3 um as a custom order, which can be delivered in most cases within 4 weeks (first order). Usually we are trying to achieve desired selectivity by playing with column type, buffer pH, buffer nature, buffer concentration and amount of ACN, in 5 years we never failed to achieve desired results.

[XL]

The most important aspect of any separation is selectivity, which is the strength of mixed-mode column. Although at beginning using one of these columns might not be as "straightforward" as using a C18 column, once we grasp the essence of the column chemistry, sometimes if not most times, method development can be much faster and easier.

In my opinoin, two factors hinder the acceptance of mixed-mode technology. First is the success and popular usage reversed-phase columns (e.g.C18) which allows many chromatographers to be able to generate good results while staying in their comforting zones. But people will appreciate it when mixed-mode columns offer solutions to the challenges that can't be addressed by reversed-phase columns. The second issue is the one brought up here - availability from multiple vendors. When I talked to the customers on the same subject, I was asked the same questions. To my knowledge, there are only two companies offering "modernized" mixed-mode HPLC columns - SIELC and Dionex. Here are some information on Dionex Mixed-Mode Columns for your information:

Silica-based mixed-mode columns:

Acclaim Mixed-Mode WAX-1 (http://www.dionex.com/en-us/webdocs/488 ... 021407.pdf)

Acclaim Mixed-Mode WCX-1 (http://www.dionex.com/en-us/webdocs/658 ... PN2024.pdf)

Acclaim Mixed-Mode HILIC-1 (http://www.dionex.com/en-us/webdocs/618 ... PN1963.pdf)

Polymer-based mixed-mode columns
OmniPac PAX100
OmniPac PAX500
OmniPac PCX100
OmniPac PCX500
(http://www.dionex.com/en-us/columns-acc ... 60681.html)

As a start, a user may try general-purpose RP columns first. If all fails, a proper mixed-mode column should be considered and it will most likely solve the problem. Once we have confidence and sufficient familarity of these columns, we can choose a right mixed-mode column right from the beginning. That is why I like to call them "general-purpose specialty" columns.

Thanks for reading and have fun!

[Kostas Petritis]

I remember that Hypersil (now Thermo) has also one RP-SCX mixed column...

[XL]

Kostas, you are right. Thermo does offer mixed-mode column called "Duet ..." It is packed with a mixture of SCX media and C18 media. Alltech (formerly) also provides mixed-mode columns which are functionalized with a mixture of ion-exchange silane and alkyl silane for the bonding. Both columns have existed for quite some time. One drawback of older mixed-mode columns is that the ratio of two functional groups tend to change over time. By comparison, the modern mixed-mode columns incorporate both ion-exchange and reversed-phase functionalities on the same ligand so that the ratio between two is constant. I believe more chemists will benefit from mixed-mode chromatography.