BRIEFING

 Chlordiazepoxide. This proposal is based on the version of the monograph official as of May 1, 2020. Based on comments received, the proposal in PF 44(5) has been canceled and is being replaced with a new proposal. It is proposed to revise the monograph with the following changes:

1. Update the molecular weight of Chlordiazepoxide in the Chemical Information section.

2. Revise Identification A to allow flexibility for the use of 197A or 197K.

3. Remove the nonspecific classic wet chemistry test in Identification C because the other Identification tests are sufficient.

4. In the Assay:

   • Update the Standard solution and the Sample stock solution preparations for clarity.

   • Include the column particle size and add a Run time for consistency with modern expectations.

   • Remove the Column efficiency requirement. The remaining system suitability requirements are sufficient.

   • Update the Tailing factor from NMT 2.0 to 0.8–1.8 to align with Chromatography 〈621〉.

   • Revise the Relative standard deviation from NMT 2.0% to NMT 0.73% to be consistent with the expectations for modern chromatographic systems.

5. In the Organic Impurities test:

   • Replace the TLC test for chlordiazepoxide related compound A and 2-amino-5-chlorobenzophenone with a more specific LC procedure. The procedure was validated using the Nucleosil C18 brand of column with L1 packing. The typical retention time for chlordiazepoxide is about 5 min.

   • Update the Acceptance criteria on the basis of comments and submissions received. Manufacturers are encouraged to submit their FDA-approved specifications to USP if they are different from those proposed in this revision.

6. Add a storage temperature requirement to the Packaging and Storage section.

7. Update the chemical information in the USP Reference Standards section.

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

 (SM4: Y. Yang)

 Case ID—SUB-2068