BRIEFING

 Caffeine. FCC 14. The Assay and Organic Impurities test were validated to align with the modernized methods in USP Caffeine monograph. The Acceptance criteria were based on the source analysis on food-grade caffeine, and align with the USP limits. On the basis of information and data received, it is being proposed to revise the monograph with the following changes:

1. In the Assay:

   • Replace the liquid chromatography procedure with a procedure validated using the Supelcosil LC-ABZ brand of column.

   • Update the preparation for Buffer, Mobile phase, and Standard solution based on the new validated procedure.

   • Revise the System suitability solution to include components that support the proposed resolution requirements.

   • Update the chromatographic system by adding the Autosampler temperature and Run time based on the proposed procedure.

   • Update the relative retention time of the components used in the System suitability solution.

   • Revise the Suitability requirements for Resolution, Tailing factor, and Relative standard deviation to be consistent with the supporting data.

2. In the test for Organic Impurities:

   • Replace the test for Other Alkaloids with a liquid chromatography procedure that share the same chromatographic conditions as in the proposed Assay.

   • Add the Sensitivity solution for Signal-to-noise ratio.

   • Add the Standard solution based on the proposed procedure.

 Additionally, minor editorial changes have been made to update the monograph to current USP style.

 This proposal is targeted for publication in the FCC 15.

 (FI: T. Xu)

 Sub Case ID: 1206