BRIEFING

 Dextromethorphan Hydrobromide. This proposal is based on the version of the monograph official as of May 1, 2020. On the basis of comments received, the previous proposal that appeared in PF 43(5) [Sept.–Oct. 2017] has been canceled and is being replaced with the following proposal. It is proposed to revise the monograph with the following changes:

1. Update the molecular weight of Dextromethorphan Hydrobromide, monohydrate, and add the chemical formula of Dextromethorphan Hydrobromide, anhydrous in the Chemical Information section.

2. Add 197A to Identification A to allow the flexibility of using either 197A or 197K.

3. Move the test for Identification B to the Impurities section as the test for Limit of Levomethorphan.

4. Replace the test for Identification B with the retention time agreement of dextromethorphan in the Sample solution and System suitability solution, as obtained in the Limit of Levomethorphan test.

5. Add Identification C for the counter ion, bromide.

6. In the Assay:

   • Update the liquid chromatographic procedure with a procedure validated using the Symmetry C18 brand of column with L1 packing. The typical retention time for dextromethorphan is about 7 min.

   • Update the Mobile phase preparation, replacing ammonium nitrate with sodium nitrate as the reagent based on the validated method.

   • Update the Mobile phase preparation as per current USP style for better clarity.

   • Update the Standard stock solution and the Sample stock solution preparations based on supporting data.

   • Update the Chromatographic system by adding the Run time based on validation data.

   • Revise the Suitability requirements for Relative standard deviation and Tailing factor to be consistent with the expectation of modern chromatographic systems.

7. Add an Organic Impurities test based on a validated liquid chromatographic procedure. The liquid chromatographic procedure is based on analyses performed with the Symmetry C18 brand of column with L1 packing. The typical retention time for dextromethorphan is about 21 min.

8. Update the Chromatographic system in the Limit of Levomethorphan test to add the Run time based on supporting data.

9. Delete the test for Limit of Phenolic Compounds because all the other tests in this proposal can adequately monitor the quality of this drug substance.

10. Replace the wet-chemistry-based procedure in the Limit of N,N-Dimethylaniline test, with a specific gas chromatographic procedure. The gas chromatographic procedure in the test for Limit of N,N-Dimethylaniline is based on analyses performed with the DB-35 brand of column with phase G42. The typical retention time for N,N-dimethylaniline is about 4.4 min.

11. Add the storage temperature in the Packaging and Storage section.

12. Add USP Dextromethorphan Related Compound A RS to the USP Reference Standards section to support the proposed test for Organic Impurities.

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

 (SM2: J. Thomas)

 Correspondence Number—C298037