Bioequivalence and Bioavailability Forum

Dear group members,
I have a query on Calibration curve acceptance criteria.
case:
We have 11 points in the calibration curve starting from STD 1 to STD 11 (lower to higher), and one blank and blank IS (blank sample with IS).

In one of the subject sample analyis run, all the standards (STD 1 to STD 11) are with in the specifications for accuracy, but, both blank and blank IS are not meeting the acceptance criteria (less 20 % of the LOQ(STD 1)) against the STD 1.

so we have removed the STD 1 from the regression and calculated the interference in the STD balnk and STD Zero samples (blank sample with IS),
against the STD 2, making STD 2 as the new LOQ, unfortunately still both blank and blank IS are not meeting the acceptance criteria against the STD 2, at this stage we have gone further and calculated the interference against the STD 3.

Making STD 3 as new LOQ, both the blank and blank IS are meeting the acceptance criteria.


Shall we accept the CC curve (truncated curve) even though 2 points (consecutives) are removed form the regression, by taking in to consideration that 75 % of the CC points are included in the regression?

One more problem is, we have 3 QCs with each batch [QC1(low), QC2 (medium)and QC3(high)], after making the STD 3 as new LOQ (truncated curve) the low level QC (QC1) (concentration) is falling below the STD 3 nominal concentration.

Shall we accept the subject samples batch even though low level QC is falling out of the truncated CC range by repeating the unknown samples, which are below the STD 3.

Please provide your valuable inputs.

Regards