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Dear All,
In a bio-analytical method using LC-MS/MS, we found after analysis of 5
subjects, that more than 10% of samples are above the upper limit of
quantification,so we have to do a partial validation with extended
range.
Now my question is can we analyze the repeat sample with the narrow
range for first five subjects? or should we reanalyze all the subjects
with extended range.
The method has not been altered even after extending the range.
Expecting valuable insights..
Regards
Dr Jacob
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Why not just validate the dilution of over-range samples by spiking a QC
at an appropriate above range level, and showing that the value times
the dilution factor is the expected (spiked) value? Analyse replicates
(n = 5 or 6) to get intra-run precision.
-Tom
Thomas L. Tarnowski, Ph.D.
Corporate Liaison & Special Tasks Director
Organizing Committee
CACO Pharmaceutical and BioScience Society
ttarnowski1.-at-.aol.com
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No, Thomas, I think partial validation with the extended range mentioned
by Jacob is the right way to do it. Otherwise, 10% of total samples out
of range is too high.
For the first 5 subjects that already have been analysed, I would think
it's fully justified by diluting those samples and reanalysing them
according to the dilution factor establish in the previous validation
method so you don't have to repeated all samples for those subjects.
Zhengguo
Zhengguo Xu
Bioanalisis y ADME Desarrollo
xzhengguo.at.esteve.es
Parc Cientific Barcelona
C/ Baldiri Reixac, 4-8
08028 Barcelona
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The usual approach as described by Tarnowski would be to validate
dilutional linearity using QCs prepareord well above the range
approximating the conc of the unknown., and or by including a dilutional
QC on the plate with samples requiring a dilution above what had been
validated. IF you extend the range you will need to re validate the
ULOQ and the HQC, the latter for stability as well as accuracy and
precision. Extending the range will also require resetting of the MQC
as well, since it will no longer be near the mid popint of the range.
It is simpler to run the dilutional linearity or integrity and possibly
develop some dilutional QC to run with unknowns
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Dear Sir
You can do the dilution integrity parameter and if it is following the
limits as per regulatory . You can dilute the same samples and reanalyse.
Thanking you
PRASHANT
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