Little thing which changes almost everything in EEU [Bioanalytics]

posted by Beholder  – Russia, 2018-10-18 11:08 (2101 d 11:26 ago) – Posting: # 19464
Views: 5,255

Hi to everybody!

Recently (IMHO, too late for me), I have revealed that EEU BEQ GL has interesting note in validation chapter which is not presented in EU BEQ GL, namely:
“Lower limit of quantification
14. The lower limit of quantification (LLOQ) is the lowest concentration of analyte in a sample that can be reliably quantified with acceptable accuracy and precision. The LLOQ is considered to be the smallest standard calibration sample (as indicated in the “Accuracy” and “Precision” subsections of this section). In this case, the signal of the analyte from the sample with the LLOQ must be not less than 5 times greater than the value of the blank sample. The LLOQ cannot be higher than 5% of Cmax (the minimum Cmax value from the entire sample of subjects) ).”

EU GL states the same but without blue text.
  1. it is quite “butthurting” since we need to set LLOQ before analyzing biosamples, but EEU BEQ GL asks to set LLOQ according to minimal Cmax from the entire sample of subjects but not the average Cmax. It may lead us to following steps:

    1. set the Cmax in advance
    2. analyze biosamples
    3. if you are not lucky and your LLOQ higher than 5% of minimal Cmax of any subject in the study, what is quite possible because of high variability of Cmax, revalidate your LLOQ with lower value
    4. analyze biosamples again

  2. it is also quite possible that there will be no opportunity to lower the LLOQ due to limitation of the LC/MSMS instrument.

What do you do in case when LLOQ higher than 5% mean Cmax? I mean in EU countries.
What is your opinion, where it could came from? Any old EU BEQ rule?

Im quite surprised that the sentence about minimal Cmax was not excluded during public consultations.

Edit: EEU GL linked. [Helmut]

Best regards

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