Bioequivalence and Bioavailability Forum

Dear All,

Happy New year

I wish to have inputs on the following issue

1. We are currently working on a Drug-Drug Interaction study where Digoxin is the substrate & X is the Perpetrator.

2.During method development we observed around 12-16% interference from Digoxin deuterated (D3) IS at the RT of Digoxin drug. There seems to be no source for D5 or D7 or D11.

3. Inspite of this interference, all the QCs (100%) (Spiked with only Digoxin & Digoxin + X) are meeting the acceptance criteria.

4. Two different sources of Deuterated IS were tested and results are similar.

5. The LOQ that we have selected is 5% of reported Cmax and there is no possibility to increase the same considering guideline recommendations.

6. Digoxin forms an adduct with Ammonia.

7. The MRM pairs are Drug (798.4 / 651.4) & Digoxin D3 (801.4 / 654.4)

8. Mol.wt for Digoxin is 780.94.


My question

1. Would it be advisable to proceed with the validation and will this have impact during sample analysis since all the samples will be spiked with IS.

2. Is there an alternate approach to this scenario ?

Kind Regards
Chirag