Bioequivalence and Bioavailability Forum

Hi community,

I am posting these questions for getting clarification, to know the industry practice and the regulatory acceptance in the following two different cases.

case 1.
For FDC formulations like Memantine & Donepezil, metronidazole and Tetracycline, Amlodipine & celecoxib, etc with simultaneous analysis in bioanalytical. Already we have proved selectivity, P&A, and all matrix stabilities in validation.

whether a specificity experiment has to be performed in validation? i.e., spiking the ULOQ concentration or anticipated cmax concentration in LLOQ and blank. or other approaches.

case 2.
In a study design like Fluphenazine hydrochloride (To prevent severe dystonia, consider administering benztropine tablets before and during the study duration) concomitant medication is administered, in such cases of studies during validation whether specificity i.e., spiking the ULOQ concentration or cmax concentration in LLOQ and blank proving is sufficient or all matrix stabilities in presence of the concomitant drug is required.

During subject sample analysis whether QCs should have both analytes of interest and the concomitant drug Cmax spiked.

Kindly share your practice and inputs.

---

Edit: Please don’t post twice. I deleted the other post. [Helmut]