SPDS EXPERT REVIEW PANEL

C. Is there information demonstrating that the

• The sample preparation, as written, will comfortably address the lower end (50 mg/g) of the analytical range. However, for the upper stated range (750 mg/g) of kavalactones will necessitate a roughly 100-fold dilution. For flavokavains, a two-fold dilution will be necessary to accommodate the upper end of the range. Method does not explicitly address this, but it is a fairly easy addition to make. • Recovery was not addressed in a satisfactory manner, so it is irrelevant • Precision study was performed using mixed standard. This is unconventional to the point of unacceptable. • Intermediate precision was not performed.

method performs within the SMPR Method Performance REquirements table specifications for all analytes in the SMPR applicability statement? If not, please specify what is missing and whether or not the method's applicability should be modified. A. Based on the supporting information, were there any additional steps in the evaluation of the method that indicated the need for any additional precautionary statements in the method? B. 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. C. 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. D. Based on the supporting information, is the method written clearly and concisely? If no, please specify the needed revisions.

IV. General Submission Package

No

• Typically, system precision should be specified, but even if not, it will be performed by well-trained analysts. • Given the chromatography at hand, resolution between the critical pair of yangonin and desmethoxyyangonin would be a desirable parameter to specify.

Not applicable; see IV(B).

Can use some polishing of the language, but given the more substantial shortcomings, it would be unwise to address method details at this time