Bioequivalence and Bioavailability Forum

Hi chandru,

❝ How to evaluate the effect of concomitant medications during validation?

Wow, that is actually a great question, and a controversial one.

Some CROs believe that when they do LC-MS/MS they don't have to evaluate it. Interference is impossible, there would never be an interfering transition, testing for it is a waste of time, inteference like ion enhancement has never been seen, and some singing and dancing to that tune.

The better CROs, and here better is in this regard a purely subjective term reflecting just my personal opinion, will test A+P by spiking the QCs at roughly Cmax levels they get from the literature (incl. prescribing info, SPCs, PARs) along with a check of interference on blanks. Some will do the spiking experiment individually, and some will do it with a cocktail. Both approaches seem to be widely accepted by agencies.
It is furthermore becoming a proper practice to have an SOP in place so that the lab is informed of any concomitant meds that are given, and if a drug has been given which wasn't part of the validation, then there will be an adhoc interference experiment for that drug (non-cocktail type).