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Dear Members
This is with regard to use of internal standards in LCMSMS
bioanalytical techniques. During method validation and subject 1 to 4
plasma sample analysis, Metoprolol succinate was used as IS. Since it
got exhausted, we used Metoprolol tartrate as IS from subject 5 to 12,
with necessary corrections for molecular weight. is this an acceptable
practice?
Request your valuable inputs on the same.
Thanks and regards
Krishnamurthy Rao
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Dear Member
Its always necessary to quote the "free-base" concentration of an
analyte being measured in biological fluids despite its "salt"
formulation. This is probably not so critical when a compound is used
as the internal standard. Did you account for the "free-base" when
preparing your internal standard solutions? If so, there is no
problem. The final stock and working standard solutions would be the
same.
If not, In this instance I would investigate its % recovery and
compare the succinate to the tartrate formulation from your matrix. As
a result a linearity check of your calibration curve with some
freshly prepared QC's should also be performed and compared. I would
serious doubt any major differences unless some ion suppression may be
observed in your ion source.
Sincerely
John.
Dr. J. Odontiadis
Senior Scientist (Bioanalytical)
RDDT Pty., Ltd.
School of Medical Sciences
Building 223 Level 2 Rm 47
RMIT University Bundoora (West) Campus,VIC 3083 Australia.
E: john.odontiadis.at.rddt.com.au
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Dear Krishnamurthy,
My expectations regarding change of internal standard in an LCMSMS
method to a different chemical species would require at least partial
validation, including collection of precision and accuracy data and
matrix effect.
Tom
Thomas L. Tarnowski, Ph.D.
Bioanalytical Development
Elan Pharmaceuticals, Inc.
800 Gateway Boulevard
South San Francisco, CA 94080
thomas.tarnowski.-a-.elan.com
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The following message was posted to: PharmPK
Dear Krishnamurthy,
I think it is not supposed to do in such
a way. At least you have to perform and document the partial validation
for that.
With Regards,
Veeravalli Vijaya Bhaskar,
Research Associate,
Aurigene Discovery Technologies Limited,
Bioanalytical Division,
Bangalore,
Email: vijayb.-at-.aurigene.com
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The following message was posted to: PharmPK
Krishnamurthy: The free base or the free acid is what you are
measuring so
that the source salt form is secondary. That being said you must
demonstrate that the new preparation is not dissimilar (is equivalent)
to
the reference preparation. This is a direct comparision and not an
historical one. You must also consider returns on the test article or
metabolite in the comparision, since counter ions from the IS may have
an
effect on the measurement. If the new material is not dissimilar
(equivalent) to the reference you are good to go.
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Dear John Odontiadis,
If the percentage recovery for tartrate and succinate is different
then we will have to analyze the previous subjects also because due to
that it might give different concentrations for remaining subjects
which may lead in wrong conclusion for PK studies
Abhijit Kakad
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