Bioequivalence and Bioavailability Forum

Dear Geokad!

❝ [...] two following questions:

Very good ones!

❝ 1-During interference evaluation from OTCs in method validation, do we

❝ have to test for their metabolites?

I think we have to distinguish whether samples are coming from a controlled phase I PK study (BA/BE, food, interaction, blahblah), from phase II/III or 'the field' (clinical practice, TDM,...).
In almost all phase I protocols I have seen intake of OTC drugs was prohibited for a certain time interval before the first dose. OK, that's no guarantee...
You can exclude most interferences with your analyte by common sense (comparing lipohilicities, and pK-values). If you have a selective detector (fluorescence, MS, MS/MS) you shouldn't bother that much. On the other hand metabolites are generally more hydrophilic than the parent and appear earlier in an RP-system...
Many people use a pragmatic approach: headache is commonly seen in PK studies (not due to the drug, but to the 14 hours fast, the clinical setting, 'bad' sleep, repetitive blood sampling, etc.). Therefore most protocols allow for administration of e.g. paracetamol/acetaminophen. The analyst should test for a potential interference and give his/her OK. If an interference with the analyte is seen another painkiller has to be selected and tested. To be honest, I have never seen anybody testing for metabolites.
In practice sometimes large interferring peaks are seen in chromatograms (especially in multiple dose studies, when the saturation phase was done in an out-patient status and volunteers take drugs...). This is a little bit tricky, but often a slight modification of the method + partial revalidation does the job.

❝ 2-Does anyone test the interference coming from contraceptives? if yes

❝ which ones and what is the procedure?

I haven't seen that - but again based on the physicochemical properties of the contraceptive(s) and your analyte I would follow common sense.