BRIEFING

 Omeprazole. This proposal is based on the version of the monograph official as of May 1, 2020. It is proposed to revise the monograph with the following changes.

1. Add 197A to Identification A to provide the flexibility of using either 197A or 197K.

2. Revise the Relative standard deviation requirement in the Assay from 1.0% to 0.73% to align with Chromatography 〈621〉.

3. Revise the test for Organic Impurities as follows:

   • Add an equilibration step in Table 1 and delete the statement "Return to the original conditions, and re-equilibrate the system for about 10 min."

   • Add Omeprazole related compound F and G mixture stock solution 1 and Omeprazole related compound F and G mixture stock solution 2 to assist in the preparation of the System suitability solution.

   • Update the preparation of System suitability solution to include omeprazole related compound F and omeprazole related compound G in support of the proposed revision.

   • Update the note for solution stability in the System suitability solution.

   • Revise the concentration of the Sensitivity solution to adequately establish the system sensitivity to quantify the omeprazole related compound F and omeprazole related compound G.

   • Under the Chromatographic system, Detector, include UV 295 nm used to quantitate omeprazole related compound F and omeprazole related compound G.

   • Add a note and Table 2 for relative retention times in the System suitability section.

   • Add Resolution criterion for omeprazole related compound F and omeprazole related compound G in the Suitability requirements.

   • Update the equation in the Analysis section to exclude omeprazole related compound F and omeprazole related compound G.

   • Add an equation to calculate the amounts of omeprazole related compound F and omeprazole related compound G in the Analysis section.

   • In the Acceptance criteria:

     • Add a reference to User-Determined Reporting Thresholds 〈477〉 for flexibility and delete the statement for the disregard limit.

     • Update the table number and list the acceptance criteria for specified impurities and unspecified impurities, including omeprazole related compound F, omeprazole related compound G, and total impurities.

4. Delete the nonspecific Completeness of Solution test, as other test procedures and requirements in the monograph can adequately establish the quality of the drug substance.

5. Delete the nonspecific spectrometry based Limit of Omeprazole Related Compounds F and G test. The currently official HPLC based Organic Impurities test is validated for quantifying omeprazole related compound F and omeprazole related compound G using the Symmetry C8 brand of column with L7 packing. The typical retention time of omeprazole is about 21.4 min, with omeprazole related compound G and omeprazole related compound F eluting at 33 min and 35 min, respectively.

6. Add USP Omeprazole Related Compound F and G Mixture RS to the USP Reference Standards section based on the proposed Organic Impurities procedure.

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

 (SM3: M. Jonnada)

 Case ID—SUB-437