Froced Degradation Sample Prep

[Chicama]

I am preparing samples for forced degradation tobe monitored by HPLC and I have some questions:

The API is not soluble enough in acid and base can I use an organic solvent mixed with acid and base? what organic solvent is not recommended? I heard the structure of the API influences the selection of the organic solvent to avoid further degradation, can anyone explain how? Also can photodegradation be performed in any glass container or is there an specific one? Thank you very much

[paulw]

Generally I make a stock for forced degradation, then prepare all degradation solutions off of that. If you have solubility in your stock, you should have solubility in your final solution. In the case of acid and base, it is always a good idea to bring the solution back to the original state, i.e. if you use 1 mL of base to do the degradation, then add 1 mL of an acid of the same normality to the solution after the degradation time.

Acetonitrile in a low concentration shouldn't affect your ability to perform the degradations, just make sure that the standard preparation you are doing alongside is also exposed to acetonitrile.

Methanol is compatible with either acid or base, however Methanol can give you some interesting interactions, particularly if you have an ester or carboxylic acid. You don't want to be making methyl esters just for fun.

Just don't perform the photodegradation in a low actinic container and you should be fine. (Sorry, couldn't resist)

[HiteshInamdar]

Hi Chicama

There is no thumb rule for "How to go for force degradation study". Main aim of this study is to show your analytical method is rugged even in case of worst sample (highly degraded).

I generally make my API soluble in diluent and then I expose to various condition. Generally, It is recommended to make the final pH of the solution near to your mobile Phase, which keeps unwanted chromatographic related problem away. ex. If you are going for Acid degradation as you add 1 mL of acid it is recommended to neutralize that solution by same normality and quantity of base. If u don't do so then it can make a Column performance go down.

"what organic solvent is not recommended?"
As such there is no specific guideline for Forced degradation study. So you can use any Organic Solvent, only thing is your Compound should be soluble and compatible with that solvent. Some times due to incompatibility, precipitation occurs, which gives absurd mass balance results. A care should be taken while using Acetonitrile as it tend to precipitate with inorganic buffer.

"Also can photodegradation be performed in any glass container or is there an specific one?"
Photo-degradation generally performed on Transparent, Low actinic and Completely covered Glassware's. This will give you the exact Information on Photo-degradation kinetics.

[shadow]

How about for drug products such as transdermal patches, do we need to extract drug and RS first before exposing it to degradation conditions or can we just place the patch in degradation conditions knowing these would not extract the drug or RS threfore causing little to no degradation? Any advise would be appreciated.