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By TS on Thursday, July 8, 2004 - 02:33 pm:
For a stability-indicating method, I understand that all degradants/impurities must be separated from the peak of interest. Do the degradants/impurities also need to be separated from themselves and do they need to be quantified and/or identified? Is there any FDA guidance or USP reference which talks more about these points? Specifically, I am referring to OTC monograph products. Any help would be appreciated. Thanks.
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By rob burgess on Friday, July 9, 2004 - 12:21 am:
For a stability indicating assay method, the degradants/impurities do not have to be sepearated from themselves, only the main peak as you have stated. This obviously makes method development that much easier.
However, an impurity method requires that all impurity peaks be seperated from each other so that they can be quantified individually. In reality this is a very dificult thing to do as an impurities are very closely related to the main peak, and because of the greater need for sensitivity, peaks are often at very different heights to the main drug peaks. Hence you are in affect overloading the column to attain sensitivity which is to detriment of resolution.
In 7 years of working in the pharmaceutical industry I have never seen a method that will totally baseline resolve all impurity peaks from each other (and the main drug peak) with high sensitivity. Thus often a compromise has to be made between sensitivty and resolution. However, thats not too say that such methods are inadequate (they can't be as they get through the registration process!).
The FDA, USP, EP and ICH undoubtedly gives some guidance. How useful anyone interprets these guidelines is another debate. Try also LC-GC columns on the topic. They are often useful and give more practical advice.
For a stability-indicating method, I understand that all degradants/impurities must be separated from the peak of interest. Do the degradants/impurities also need to be separated from themselves and do they need to be quantified and/or identified? Is there any FDA guidance or USP reference which talks more about these points? Specifically, I am referring to OTC monograph products. Any help would be appreciated. Thanks.
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By rob burgess on Friday, July 9, 2004 - 12:21 am:
For a stability indicating assay method, the degradants/impurities do not have to be sepearated from themselves, only the main peak as you have stated. This obviously makes method development that much easier.
However, an impurity method requires that all impurity peaks be seperated from each other so that they can be quantified individually. In reality this is a very dificult thing to do as an impurities are very closely related to the main peak, and because of the greater need for sensitivity, peaks are often at very different heights to the main drug peaks. Hence you are in affect overloading the column to attain sensitivity which is to detriment of resolution.
In 7 years of working in the pharmaceutical industry I have never seen a method that will totally baseline resolve all impurity peaks from each other (and the main drug peak) with high sensitivity. Thus often a compromise has to be made between sensitivty and resolution. However, thats not too say that such methods are inadequate (they can't be as they get through the registration process!).
The FDA, USP, EP and ICH undoubtedly gives some guidance. How useful anyone interprets these guidelines is another debate. Try also LC-GC columns on the topic. They are often useful and give more practical advice.
