Bioequivalence and Bioavailability Forum

Dear Deepak,

❝ I have developed and validated new method (changes primarily include [...] parent analyte spiked in plasma in presence of metabolite for all experiments) and performed study sample analysis with new method.

I'm not sure I understand. Did you measure the metabolite too ? If yes and as rightly pointed out by VKB2207, you need long-term stability data for the metabolite anyway, so you old data will not save you. If not, why did you add the metabolite for all experiments ? Can you give us more details on the structure of the metabolite compared to the parent compound (primary or secondary metabolite, risk of back-conversion etc.), and the levels of concentration of the metabolite compared with the parent ?

❝ However I am unable to finish LTS experiment for required duration with new method.

Is this just because the sponsor is in a hurry and wants the report last week, or are there other reasons ?

❝ Can I use long term stability data of old method as supportive data for my usfda study submission?

Long-term stability in matrix is independent from the bioanalytical method used: if the analyte is stable for 3 months with method A it will also be stable for 3 months with method B. The FDA and EMA requirement to test for the stability of all analytes spiked together in case several drugs are given to a subject, even if stability data are available for each analyte separately (e.g. drug/drug interaction studies), is highly disputed by industry and regularly discussed at bioanalytical conferences. I didn't hear of an extension of this FDA/EMA requirement to non-measured metabolites.

However the storage conditions are important (not just the temperature, also the type of tubes used due to possible adsorption), and you should check they were the same in the old and new method.

But the final answer to your questions depends on your answer to some of mine