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3. Is there information
demonstrating that the method
performs within the SMPR Method
Preformance Requiements table
specifications for all analytes in the
SMPR applicability statement? If
not, please specify what is missing
and whether or not the method's
applicaiblity should be modified.
For linearity ‐ yes.
For analytical range ‐ mostly, but limited to 25%, but does not meet the range
requirements of greater than 50% (there are products out there that high).
For LOQ ‐ the SMPR specifies that the LOQ should be less than 0.1% in the sample
materials. The LOQ specified in this method is ug/mL. using the lowest dilution for
this method the curcumin (which is the highest LOQ ‐ 2.86 ug/mL) would back
calculate to 0.0143 %, assuming that the sample mass is 500 mg, which is not
actually specified in the method (taken from optimization information). So Yes, LOQ
is sufficient.
Accuracy/Recovery ‐ Not specified in the document.
Repeatability ‐ As specified above the methodology used biases the repeatability
data due to between injection and between sample being treated as replicates.
Additionally, the CurcuViva product is consistently not within the <5% RSDr as
specified in the SMPR. All other products appear to meet SMPR repeatability
requirements, but I would recommend re‐treating the data and only taking the
triplicate measurements to ensure true repeatability is obtained.
Some of the other dietary ingredients listed in Table 2 have also not been used in
any of the multi‐component products.
1. Based on the supporting
information, were there any
additional steps in the evaluation
of the method that indicated the
need for any addional
precautionary statements in the
method?
No
2. Does the method contain
system suitability tests or controls
as specified by the SMPR? If not,
please indicate if there is a need
for such tests or controls, and
which ones.
The system suitability requirements of the SMPR specifies that check standards
should be run throughout the validation ‐ in the case of this run, there were only
blank samples, but no QC/check standards run. System suitability was not performed
at the beginning of the validation either to ensure that the system was working
properly.
3. Is there information
demonstrating that the method
system suitability tests and
controls as specified in the SMPR
worked appropriately and as
expected? If no, please specify.
Linearity was sufficient, which would ensure that the system was suitable, but there
was no actual system suitability performed.
4. Based on the supporting
information, is the method written
clearly and concisely? If no, please
specify the needed revisions.
There is some information that is missing in the method preparation. The actual
sample masses of the samples (or atleast recommended ranges of masses) are
missing. This would cause a lot of confusion adopting the method. Additionally,
several different extraction volumes were used. It would make sense to specify
which volumes were suitable for what types of samples (or what expected ranges or
ingredients). As for softgels, the results obtained from this would likely be
mg/capsule, rather than mg/g, as you should not typically include the mass of the
softgel in the analysis.
5. Based on the supporting
information, what are the
pros/strenghts of the method?
The strengths:
simple sample preparation
fast chromatographic separation
baseline separation of the curcuminoids
suitable for many sample types, ingredients, etc.
6. Based on the supporting
information, what are the cons
/weaknesses of the method?
The weaknesses:
lack of sufficient information for sample preparation
requires a significant amount of glassware
extraction solvent selection (see below)
IV. General Submission Package