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Dear All,
We have got a compound with COA (certificate of Analysis) from USP with two
different % purity of the compound.the label on the compound reads Like 99.99%
should be considered for UV/Vis applications and 99.93% should be considered for
the chromatographic applications.
We have already done the validation with 99.99% purity, our's is a bioanalytical
method with LC-MS/MS. My question is, can we accept the data with said
purity (99.99%)? or should we change the entire data with other purity (99.93%)?
Also i would like to know why the same compound is having different purity for
different applications?
Expecting valuable insights.
Thanks in Advance
Jacob.
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Jacob,
USP Reference Standard is for use with the specific USP monograph and usually
comes with a statement to the effect that its suitability for non-compendial
applications is solely the responsibility of the user. So perhaps you should
consider whether the material is at all suitable for the specific type of MS-MS
detection you are using. (You may want to compare with results from the LC-UV
method). Usually the USP only provides purity statements for a Certified
Reference Material, (CRM). If you are refering to a CRM, then the methodologies
should be well documented on the Certificate you have, including signatures of
people you could contact for further insight if you want. However, different
analytical methods often have different specificities, so it is common for
specific materials to interfer with one analytical method and not another.
Regards,
Frank Bales
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Regarding two %purity values on a COA, perhaps the first was determined by
weighing a known amount, determining the absorbance, and using a known
extinction coefficient to calculate the amount present in the amount weighed.
And perhaps the second was determined from a chromatographic determination where
the area of the peak interest was determined as a percentage of the sum of all
peak areas in the chromatogram.
For most bioanalytical purposes, the difference between the two values is
negligible, as is the difference of either from 100%. In such cases my groups
over many years have often reported the applicable COA purity in the validation
and the bioanalytical reports (e.g., as 99.93%) and stated that the purity was
used uncorrected (i.e., as 100%) in calculations, without any correction factor
to account for the slight difference from 100%. I have never had this practice
challenged by regulatory reviewers, and anyone reviewing the data could apply
the factor to see what difference would ensue in any given calculation. It is
likely that errors and confusion in applying the very small correction factor to
all calculations would cause more issues and potential discrepancies than using
the value as 100% and stating so up front.
It is also useful to have the practice documented in a relevant SOP (e.g., state
that for compounds with %purity values >99.0% [or pick another limit], values
may be used as 100% in calculations, with no correction factor; such cases will
be noted in the corresponding Reports).
In your case where you have already used a very small correction factor (0.01%)
for the 99.99% COA purity, it might be simpler and preferable to use 100%,
rather than have to answer why you chose the 99.99% value, have to remember in
the future to do it the same way (what happens when the next ref std is slightly
different?), or switch to the 99.93% purity. If you choose to stay with the
99.99% value that you already used, be sure to be very clear in the relevant
Report(s) to state what you used.
In summary, the differences in values in question are very small and
insignificant in bioanalytical determinations where %cv and %biases of 15.0% are
acceptable; the main point is to be transparent and consistent and enable
reconstructability.
-Tom
Thomas L. Tarnowski, Ph.D.
Corporate Liaison & Special Tasks Director
Organizing Committee
CACO Pharmaceutical and BioScience Society
ttarnowski1.-a-.aol.com
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The following message was posted to: PharmPK
Dear Jacob
Yes, you should revalidate your method with the purity 99.93%. Because
chromatography condition is always more sensitive then UV/Vis application.
Pradeep kumar
Ranbaxy research laboratory
Gurgaon Haryana india
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Dear Thomas,
You are right this factor is negligible and it is not challenged even in court
cases in drug analysis.
Dr Zafar
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