By Kati on Wednesday, October 9, 2002 - 11:42 pm:

I was told by three "chromatography people" that one of the ICH guidelines sets the conditions for forced degradation (0.1N acid, base, and 3% H2O2). I looked at all ICH guideline that I found, but I did not find that one that I needed. Could anybody help me with the exact code/number/revision/date of the guideline where I could find these conditions?

Thanks!

Kati

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By Anonymous on Thursday, October 10, 2002 - 12:58 am:

You can find practical guide in a book "Analytical chemistry in a GMP enviroment" (Ed. J.M. Miller, J.B. Crowther, Wiley Interscience Publication). The reference for forced degradation J. M. Green, A practical guide to analytical method validation, Anal. Chem. 60, 305A-309A (1996)

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By Anonymous on Thursday, October 10, 2002 - 06:37 am:

There was also an LC-GC article on how to perform forced degradation in late 97 or early 98. I apologize for not having the compelte reference.

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By Anonymous on Thursday, October 10, 2002 - 08:04 am:

ICH provides few specifics regarding forced degradation studies. Unfortunately, there is no industry standard either. While I have seen similarities in the way different companies approach stress studies, I have seen many differences in the design of stress studies as well. This is especially true with stress severity. Many people agree that only reasonable stress should be used whereas others propose that 5-10% stress must be achieved regardless of the severity of the stress conditions.

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By mike carolus on Thursday, October 10, 2002 - 10:40 pm:

I found and article in Pharmaceuitcal Technology Feb 2002 on forced degradation. If you want I can email the article to you. I hope this reference helps.

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By Kati on Thursday, October 10, 2002 - 11:22 pm:

Thanks everybody the answers!

It seems that no ICH guideline defines 0.1N HCl and NaOH? I have not found these conditions but, as I wrote, 3 different people told me that it was written "somewhere".

Mike, I would appreciate if you sent me the Pharmaceutical Technology article.

Thanks again!

Kati

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By labcat on Friday, October 11, 2002 - 01:47 am:

I found very useful also this article:
"Guidance on Conduct of Stress Tests to Determine Inherent Stability of Drugs"
S. Singh; M. Bakshi
Pharm. Technol. On-line, April 2000

As fas as I know, stress testing is adviced/required in differente guidelines (Stability testing of drug substances and drug products, CDER draft of 1998; ICH-Q1A 1994; ICH-Q2B 1996; probably several others...) but I too wasn't able to find a statement like "0.1N HCl or NaOH". Anyway, they are useful starting points.
Good "stressing"!

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By Kati on Monday, October 14, 2002 - 05:56 am:

Dear Labcat,

Could you write me the volume and page Nº of the article you mentioned above?

Thanks!

Kati

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By Tom Mizukami on Monday, October 14, 2002 - 04:45 pm:

Hi Kati,

Don't forget temperature and light, these both need to be studied per ICH. For drug product you also need to run placebo controls to ensure that you don't have an interference with an excipient degradant. I don't think there is specific guidance as to conditions because to some degree it will depend on your analyte and what degradation pathways are available.

We LIKE to see 5-10% degradation and will do some adjustment of conditions to reach this target. I have seen many companies use more agressive conditions for drug substance but normally stop at some point with drug product because you will eventually just be degrading excipients.

I normally start with 0.1N HCL and NaOH for one hour then increase time and or concentration to try and get about 10% degradation. If 1 or 5M acid/base for 24 hrs produces no degradation I assume this pathway is not going to be available during stability testing and move on.

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By Pravin Karmuse on Thursday, March 25, 2004 - 04:02 am:

I am working on HPLC analysis of a new drug. There is unknown impurity is found in almost in all samples (~ 0.1%)
We have tried for isolation of that impurity but found it very difficult.
I have one sample where the assay of the drug is 95% and there is no other impurity seen on chromatogram except that impurity. (means only two peak, one for drug & other for the impurity).We have also analysed the sample for ROI & ash to confirm that there is no inorganic impurity in that sample. Also LOD & moisture containt is negligible.It meance this particular sample contains 95%of Drug and 5% of the impurity only.
Can I use the above sample for quantitation of the same impurity in other sample considering 5% containt of it?