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The following message was posted to: PharmPK
Dear list,
We are currently validating an HPLC method for detection and
quantitation of a
drug product impurity in a biological matrix. All aspects of the
validation
have been agreed upon except for Specificity. This impurity is
introduced
during manufacturing and later removed.
Our HPLC consultants (let's call them) insist that quote:
"...specificity is
not required when using a PDA detector with spectral library... which
for all
practical purposes is infallible". The library in fact contains the
molecule to
be detected and quantitated and in fact recognizes it; we also
understand their
argument except that we still think this should be validated into the
assay.
Also, the substance in question is readily available as well as an
analog
substance. Another point is that the cost and time involved in including
specificity would be negligible.
The assay is based on the USP assay for this substance and in fact it
lists the
analog substance as "resolution solution". Our HPLC consultants also
insist
that the resolution solution is not needed as part of the assay, and in
fact it
is not included in our current method.
I was wondering what the list might think about this, in particular
relating to
what the FDA's position might be on this.
Regards,
Roy
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Hi:
Specificity is the ability of the analytical method to measure the
analyte in the presence of other components that are expected to be
present. For the determination of specificity, samples are prepared
by spiking possible interfering agents (impurities, degradation
products, excipients etc.). Recovery of the analyte from the spiked
sample is compared to the unspiked sample and a percent agreement is
calculated. A percent agreement of close to 100% indicates the
absence of any bias in the analytical procedure that is caused by the
presence of interfering agents.
Based on the above definition, you will need to demonstrate
specificity of the method by spiking the biological matrix plus the
parent compound.
Satya Murthy, Ph.D.
Analytical Development
Genta Inc.,
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Not exactly true.
A specific method is one where the method of detection detects only
the analyte of interest, in the presence of all others. The others do
not generate a signal from the detector.
A selective method is one where the method of detection detects the
analyte of interest and some to all of the others present. However
the method resolves the signal from the analyte of interest from
those of the others, allowing quantitation.
Stan Alekman
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