SPDS EXPERT REVIEW PANEL

B. Does the analytical technique(s) used in the method meet the SMPR? If not, please specify how it differs from what is stated in the SMPR. C. Are the definitions specified in the SMPR used and applied appropriately in the method? If no, please indicate how the terms are used. D. Does the method, as written, contain all appropriate precautions and warnings related to the method's reagents, components, instrumentation, or method steps that may be hazardous? If no, please suggest wording or option(s). A. Are the definitions specified in the SMPR used and applied appropriately in the supporting documentation (manuscripts, method studies, etc...)? If not, please explain the differences and if the method is impacted by the difference. B. Is there information demonstrating that the method meets the SMPR Method Performance Requirements using the Reference Materials stated in the SMPR? If not, then specify what is missing and how this impacts demonstration of performance of the method.

Yes

The following definitions are misapplied:  Recovery  Precision

None necessary

III. Review of Information in Support of the Method

• Precision is done on a mixed standard. It should be performed on a homogeneous sample. • Recovery is not done at all; or rather the precision samples are used to fulfill the accuracy requirement. This is one of the most fundamental shortcomings of the method. • Intermediate precision is not done at all

• Reference material source is indicated, even though not one of those mentioned in SMPR. However, no certificates of analysis, or stated purity values have been made available, and no appropriate purity correction is performed when calculating concentrations. • Should the purity values deviate substantially from 100%, this would affect calculation of the calibration curve slopes. There is, for example, a noticeable difference in molar absorption coefficients of flavokavains A and C which is not immediately explainable by the differences in chromophores. It would be beneficial to be able to reconfirm the purity of the reference materials to eliminate any hesitations.