Bioequivalence and Bioavailability Forum

Dear Auditor,

If I understand correctly your concern:

• you validated a method with a given range (let's say 1 to 100 ng/ml)
  
• after analysing a few subjects, you realised that the range was too low, as many samples were above ULOQ
  
• you expanded the range (let's say 1, or possibly 2, to 200 ng/ml)
  
• you now wonder whether above ULOQ samples should be re-analysed with the short range (1 to 100) after a dilution, or with the expanded range (1 to 200) without dilution, and you would prefer the first option.

I think it would be OK to have the samples re-analysed with the wider range and no dilution (supposing you have re-validated the method with the new range, of course). One could object that these samples will be analysed with different conditions compared with samples from the same subject which were below ULOQ, and that it may create some disruption in the PK profiles. On the other hand you will avoid the influence of a dilution (and of possible differences in matrix effects between your subject plasma and blank plasma).

What reason made you prefer to re-analyse the samples with the initial range ?

Regards
Ohlbe