Mass Balance

Chromatography Forum: LC Archives: Mass Balance
Top of pagePrevious messageNext messageBottom of pageLink to this message  By Anonymous on Thursday, May 22, 2003 - 03:56 am:

Does anyone know where I can find some useful background information on evaluating the mass balance for a typical forced degradation study ?


Top of pagePrevious messageNext messageBottom of pageLink to this message  By Tom Mizukami on Tuesday, May 27, 2003 - 11:26 am:

There have been previous threads on this topic.

There are a few issues with performing a mass balance on stressed stability samples. In order to perform a real mass balance you need standards for all of your degradants, or at least accurate response factors for your chromatographic conditions. This may or may not be possible depending on where in your product development cycle you normally perform degradant characterization and when you validate your methods. If you have all of the standards or response factors then it is simply a matter of comparing the number of moles injected to the total moles recovered.

In specific situations some detectors might be useful like a RI, ELSD, or MS. However, robust true equilmolar response that doesn't need to be verified with standards it tough. The most useful for detecting a mass balance defect is probably a CLND, Chemiluminescent Nitrogen Detection.

In lieu of a real mass balance, I at least try to perform an area balance in an attempt to detect if we are not recovering a degradant from a column. I compare the area from a flow injection to the total area recovered from the column. Also take a good look at the flow through from the placebo and compare with the active containing sample.

I also like to start development or validation with the forced degradation studies. This way I can use the wide range scouting gradients to help ensure that I'm not leaving a degradant unretained or uneluted. Good luck.


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