BRIEFING

 Clidinium Bromide. This proposal is based on the version of the monograph official as of May 1, 2020. It is proposed to make the following changes:

1. Update the molecular weight of Clidinium Bromide in the Chemical Information section to be consistent with the USP naming convention.

2. Revise the acceptance range in Definition and Assay from NLT 99.0% and NMT 100.5% to NLT 98.0% and NMT 102.0% which is typical for a chromatographic assay.

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

4. Replace the TLC-based Identification B with the retention time agreement of the major peak of the Sample solution and Standard solution, as obtained in the Assay.

5. Add reference to Identification Tests–General<191>, Chemical Identification Tests, Bromide for Identification C.

6. Replace the titration-based Assay with a validated HPLC procedure using the Gemini C18 brand column with L1 packing. The typical retention time for clidinium is about 15 min.

7. Replace the TLC based Organic Impurities procedure with a validated liquid chromatographic procedure using Gemini C18 brand column with L1 packing. The typical retention time for clidinium is about 15 min.

8. In the test for Organic Impurities, add Table 3 in the System suitability section to present relative retention times as an aid in peak assignment. In the Acceptance criteria, Table 4 list only the limits for specified impurities, any unspecified impurity (where applicable), and total impurities.

9. Revise the TLC-based Limit of Clidinium Bromide Related Compound A test to be consistent with the FDA aproved test procedure.

10. Add USP Trospium Chloride Related Compound A RS, USP Clidinium Bromide Related Compound B RS, and USP Clidinium Bromide Related Compound C 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.

 (SM3: M. Jonnada)

 Case ID−SUB-352