Chromatography Forum

Hello,
I want to use reagent grade Sucrose and Benzoquinone(e.g. Sigma) as referance standard in place of USP standards in TOC testing. Is it acceptable by regulatory agency? If it is acceptable, what should we do to make it reasonable?
Thank you in advance.

And where is the chromatography related question?

Best Regards

Hi

From the ICH Q7a guideline:

11.17 Primary reference standards should be obtained as appropriate for the manufacture of APIs. The source of each primary reference standard should be documented. Records should be maintained of each primary reference standard’s storage and use in accordance with the supplier’s recommendations. Primary reference standards obtained from an officially recognised source are normally used without testing if stored under conditions consistent with the supplier’s recommendations.

11.19 Secondary reference standards should be appropriately prepared, identified, tested, approved, and stored. The suitability of each batch of secondary reference standard should be determined prior to first use by comparing against a primary reference standard. Each batch of secondary reference standard should be periodically requalified in accordance with a written protocol.

So essentially I would recommed to do as above ie you qualify your secondary reference standards (the reagent grade purchased) against the USP/primary reference standards.

If you do not have a standard operating procedure for handling reference standards I would recommend getting one from an audit point of view.

Many years ago, a friend of mine was analysing sucrose. As her standard, she bought the very best top quality sucrose available from one of the world's leading suppliers of fine chemicals. Names will be removed to protect the innocent.

For a laugh, she also took a teaspoon of sugar from the coffee room.

I'll let you guess which was the more pure...

Haha

Yes your right, just because it comes from a "recognised source" it does not necessary mean it is particular pure

Seen the same a few times

Guys,

Aren’t you exaggerating the matter a bit?
The poster wants to determine Total Organic Carbon perhaps in connection with some washing validation or water testing or something like that. I’ve never heard of API testing by TOC. So, all these fancy primary and secondary standards are most probably way out of target.
Another thing is why such a question should be answered by chromatography freaks such as most of us are – I am, anyway.

Best Regards

Guys,

Aren’t you exaggerating the matter a bit?
The poster wants to determine Total Organic Carbon perhaps in connection with some washing validation or water testing or something like that. I’ve never heard of API testing by TOC. So, all these fancy primary and secondary standards are most probably way out of target.
Another thing is why such a question should be answered by chromatography freaks such as most of us are – I am, anyway.

Best Regards

Yeah sorry there, you might be right there Danko, if used for purified water or water for injection it might be boarder case.

As you said TOC is typically not used for APIs, however I maintain that in GMP enviroment you should have a procedure for what goes for what reference standards.

As for answering these types of questions (more GMP, compliance etc), personally do not mind and it also somewhat an organision issue depending on where you work. As an analytical chemist in the GMP area you sooner or later tend to have to deal with similar questions as the QA department sometimes knows nothing about the more "technical oriented/boarderline questions" and simply put just signs of some stuff.

To take this example, any QA can read up on the guideline for APIs, however setting up the test protocol for reference standard depending on it use, stability etc is more a chemist thing.

Caution - chromatography-free post, if offended, don't read on...

Look at what your regulator says in the TOC method. The EP allows EP grade sucrose ( therefore any sucrose that has passed EP can be used - probably available at a few $100/Tonne . They also specify the benzoquinone as 98% minimum, with no grade specified - so any commercial product that meets that criteria can be used - just ensure suitable CoAs are available to satify your quality group..

I don't have the latest USP, but there's no reason why you couldn't purchase a good A/R grade and formally compare to USP reference standards. You would need quality signoff of the protocols before starting.

I really dislike the USP practice of repackaging cheap reagents and selling them as exorbitantly-priced "reference standards", especially of assays like TOC where purity is pretty much a non-issue, given the inherent lack of precision of the process.

They should take a leaf out of the EP, or even better the Japanese Pharmacopoeia - which makes a lot of information freely-available.

Please keep having fun,

Bruce Hamilton

Thank you for all of the help. Thank you Bruce Hamilton, krickos.

danko: Sorry for distracting you from chromatography things. I think the most talented guys are ususlly here, so I posted this subject in this domain.

Liu De