change in response

[pliva]

dear friend,
we have validated ms method for isradipine for be studies. my response for LLOQ during validation 45000 but when i performed subject sample anaysis the response drops down to almost half. still my ccs and qcs do not have any problem. all my seniors said that auditors will rise question about it and we have to justify it. we then investigate the problem and it turns out due to the methanol grade. during validation we use brand X and during subject anaysis we use brand Y. now we do not have brand X in stock. can i proceed my analysis provided the justification is due to variation of the brand? did anyone face problem like this? as for me i feel there is nothing wrong but as we are going to face the auditors from outside i just want to know the sugestions from you all.

with regard
pliva

[Uwe Neue]

How did you prove that it was the methanol? Is this only a suspicion, because this is the only thing that you found to be different between the validation study and the current study? Also, what is the difference between "subject samples" and the validation samples?

[pliva]

How did you prove that it was the methanol? Is this only a suspicion, because this is the only thing that you found to be different between the validation study and the current study? Also, what is the difference between "subject samples" and the validation samples?

yes it is due to methanol. we got one bottle from other lab and checked out with different brand. when i use the brand which we used during validation the response was almost the same but with other brand .

[pliva]

How did you prove that it was the methanol? Is this only a suspicion, because this is the only thing that you found to be different between the validation study and the current study? Also, what is the difference between "subject samples" and the validation samples?

yes it is due to methanol. we got one bottle from other lab and checked out with different brand. when i use the brand which we used during validation the response was almost the same but with other brand .

validation sample means the plasma where the drug is spiked externally and subject sample means the blood is is collected from the volunteers during clinical study.

[ZG]

If the S/N for LLOQ is still big enough (mostly at least 5), just go ahead.