BRIEFING

 Chlordiazepoxide and Amitriptyline Hydrochloride Tablets. This proposal is based on the version of the monograph official as of December 1, 2022. It is proposed to make the following changes:

1. Move the light protection requirement in the Definition section to the beginning of each test.

2. Update the molecular weight of amitriptyline in the Assay and Dissolution test.

3. Update the equations in the Dissolution test.

4. Clarify the acceptance criteria within the test for Uniformity of Dosage Units.

5. In the test for Organic Impurities:

   • Replace the thin-layer chromatography procedure with a validated liquid chromatographic procedure, which shares the same Mobile phase, Diluent, and Column as those in the Assay.

   • The liquid chromatographic procedure was validated using the XBridge C18 brand of column with L1 packing. The typical retention times for chlordiazepoxide and amitriptyline are about 4 and 22 min, respectively.

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

6. In the USP Reference Standards section:

   • Add USP Amitriptyline Related Compound A RS, USP Amitriptyline Related Compound B RS, and USP Nortriptyline Hydrochloride RS to support the updated test for Organic Impurities.

   • Update the chemical information for USP 2-Amino-5-chlorobenzophenone RS and USP Chlordiazepoxide Related Compound A RS.

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

 (SM4: Y. Yang)

 Case ID—SUB-2069