Bioequivalence and Bioavailability Forum

Dear Helmut and Ohlbe,

Many thanks for your response.

❝ Anything else that varied here, such as retention times ?

As far as I can tell from the excel file that was exported from Analyst, retention times are very consistent.

❝ By the way, how are the results of the last 6 QC samples ?

The last 6 QCs are high/medium/low/high/medium/low QCs. ULOQ is 3500 ng/ml and HQC is 2660 ng/ml, 76% of ULOQ. Actually, last 6 QCs all passed accuracy criterion with the range 93–95%. There were 2 failed QCs in the early injections (1 HQC around 82% and 1 LQC just lower than 85%).

❝ If even the last ones are passing, you could conclude that whatever is happening does not appear to have a large effect on accuracy. I'd still be concerned, ...

Yes, no large effect on accuracy for this study is expected. But as I said, I am not really concerned for this study since the formulation is crappy anyway and we are developing the new one as we speak.

What concerns me is those studies in the future. Certainly I don't want the studies conducted with this same SOP in force where runs such as the one above being accepted without any further investigation.

❝ ❝ The calibration curve is not repeated at the end of the run, so there is no way to check what's happening at the ULOQ, where you may get linearity issues due to detector saturation or ion suppression of the analyte by the IS.

❝

❝ Yep. Many CROs have the CC in duplicates only at the start of the run. IMHO, that should be avoided. I prefer to have one set of singlets at the start and another at the end.

I would make a suggestion to the CRO for the modification of their SOP to take incidence like this into consideration. One way is like you said, repeat another set of CC at the end. What else can we do to improve it?