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The following message was posted to: PharmPK
Dear All,
We have faced a situation in LCMSMS project, wherein, we found around
20 chromatograms (out of 1000 chromatograms) required Re-Integration.
It is required because of adjoining peak. However, the Height of
adjoining peak is less than 20% of drug peak height. This adjoining
peak is also observed in Pre Dose sample.
Whether it is justifiable for Re-Integrating these many chromatograms
or it is required to separate the adjoining peak by modifying
existing method.
We also wanted to know that whether there is any limit for Re-
Integrating the number of Chromatograms during subject sample analysis.
Bioequivalence criteria is met both before and after Re-Integrating
chromatograms.
Thanking You,
Regards
Dr Ashish Mungantiwar
Head-Bioequivalence
Macleods Pharmaceuticals Limited, India
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The following message was posted to: PharmPK
Dear Dr Ashish Mungantiwar,
Can't you just change your integration settings to optimize for the
adjoining peak be separated from your analyte....
Regards Bert
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Dear Dr. Ashish
The first requirement is the peak should be properly integrate to
give correct result. As per my knowledge there are no limitation for
reintegration of chromatograms. It should be documented with proper
reason as per your SOP and both the chromatograms should be available.
If you are reintegrating the chromatograms due to interference in few
subject samples only which are unknown for you. It should not be
objectionable. But if you observe these trend for all subjects you
need to redevelop the method to separate the adjoining peak and
partial validate the method.
The other option is that if you found that the interfering peak in
Pre-Dose sample, set integration parameter for all the batch in that
way so Pre-Dose sample will not show peak but all other peaks
integrated properly and document the reason. That time you need not
to do reintegration. But it is again only for few subjects not for all.
Hope this help.
Manish Jain
Group Leader-Bioanalytical
Wellquest Clinical Research, Mumbai
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The following message was posted to: PharmPK
Dear Dr. Mungantiwar
From the multiple bioanalytical CRO feed backs and the recent 483
records filed by US-FDA, it is potent to hold high standards in
reviewing and accepting the bioanalytical data/results. This is
especially true for the BA/BE studies.
While the number of the re-integration is a factor, the most important
issue one has to determine is not it but the impact(s) from this
potential interference in the assay to the integrity of the study
data/results. Based on your description, the interference may be
significant (as high as 20% peak high of the analyte) and repeatable.
Adjoining peaks imply possible interference in the assay, hence,
casting a potential doubt to the integrity of the concentration
data/results. Good scientific practice and good laboratory practice
would require you to understand what cause the interference in the
assay (if possible), what is the impact and the extend of the impact
of the interference to the study data/results.
I would suggest to lunch an investigation per your SOP, and
communicate the fact and findings to your sponsors immediately. Based
on the outcome of the investigation, remedy should be proposed, agreed
upon and executed. The remedy can range from simply re-integrate
affected chromatograms to re-develop/re-validate the assay and
re-analyze the samples. The investigation should be carried out per
your established SOP; process, reason for action taken and results for
the investigation should be properly documented and supported by SOPs
and good scientific rationale(s).
Good luck,
Ta Kung Chen, Ph.D.
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