I need to do a forced degradation on a normal phase method (i.e. I have a nonaqueous sample.) What is the "textbook" way to do the acid, base and oxidative degradations to meet USP/ICH guidelines?

If the HPLC method used for the analysis of the samples,obtained in forced dergadation study is a normal phase method,you should follow same simple rules: 1. Dissolve your sample in suitable organic solvent(we usually use dioxane)at higher possible concentration ( try to get tens or more mg/mL level), than add 1-10%(v/v) of acidic(or basic or H2O2) water solution ( usually 1N)- find an appropriate ratio in order to avoid sample precipitation or phase separation.
2.Perform the degradation,than take an aliqoute of the obtained solution and dissolve with your mobile phase to ~concentration, prescribed in your analitycal procedure ( usually ~1-5mg/mL), i.e. degradation sample in water/dioxane solution should be diluted with the mobile phase in at least 1:50 ratio(you have to keep the "elution power" of your sample preparation close to mobile phase used in original method).
We have used this approach succesfully
in our laboratory.Of course, corrections of blank
for the present of dioxane/acid etc. in sample preparation should be done.

Good luck!
Dr.A.Weisman
Chemagis Ltd, Israel