SPDS EXPERT REVIEW PANEL

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. 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

Initially, the reference material of the SAMe was not indicated. Is it USP quality or not? Also the Cat No should be indicated too, as in SMPR requirement.

Analytical ranges and performance requirements seems that the proposed method met with the requirements. However, the units should be changed in the proposal. In SMPR all units given as mg/g. In contrary to this, author of the method given all results in ug/mL etc.

IV. General Submission Package

The proposal prepared in a different way. The necessary information are not easily reachable and understandable. Technical revision required for this proposal.

Based on the SMPR that the authors should be shown the selectivity by using mentioned products in Table 4 and 5. In the proposal, newly developed method does not meet with the system suitability requirements. The authors illustrated related information in published paper but the conditions of the method which currently proposed was different with the published paper in 2002. Because of this reason, The products mentioned in Table 4 and 5 should be analysed and demonstrated with chromatogram. Also, according to the SMPR, "Suitable methods will include blank check samples, and check standards at the lowest point and midrange point of the analytical range. A control sample must be included." Related data should be supported by the chromatograms.