BRIEFING

 Amiodarone Hydrochloride. This proposal is based on the version of the monograph official as of December 1, 2020. It is proposed to revise the monograph with the following changes:

1. In the Chemical Information section:

   • Update the molecular weight.

   • Remove the IUPAC name and CAS number of amiodarone free base since the free base is not utilized in currently marketed products.

2. Revise the acceptance range in the Definition and the Assay from NLT 98.5% and NMT 101.0% to NLT 98.0% and NMT 102.0%, which is typical for a chromatographic assay.

3. In the Identification section:

   • Revise Identification A to allow the flexibility of using either 197A or 197K.

   • Rename Identification B as Identification C and add a new Identification B based on retention time agreement, as obtained in the Assay.

4. In the Assay:

   • Remove the Column efficiency requirement, as the other System suitability requirements are sufficient.

   • Revise the Relative standard deviation requirement from NMT 1.0% to NMT 0.73% to be consistent with the expectations for modern chromatographic systems and supporting data.

5. In Organic Impurities, Procedure 1:

   • Replace the TLC-based test with an HPLC-based procedure. The liquid chromatographic procedure was validated using the Dionex IonPac CS17 brand of column with L77 packing. The typical retention time for amiodarone related compound H is about 15 min.

6. In Organic Impurities, Procedure 2:

   • Replace the Standard stock solution with the System suitability stock solution and the Standard solution with the System suitability solution. Delete USP Amiodarone Hydrochloride RS from both the preparations, as it is not needed to establish System suitability criteria. Add the target concentration of 0.2 mg/mL for each component to the System suitability stock solution.

   • Add a new Standard solution to support the Relative standard deviation requirement under the System suitability requirement.

   • Add the Sensitivity solution to support the addition of the Signal-to-noise ratio requirement under the System suitability requirement.

   • Rename the current Table 1 to Table 2. Add a new Table 1 and add a Note in the System suitability section to present relative retention times as an aid in peak assignment.

   • Update the trivial names and chemical names for all the impurities in Table 1 and Table 2 to be consistent with USP style.

   • Remove "hydrochloride" from "Amiodarone hydrochloride" in Table 1 because this chemical name refers to the analyte.

   • Update Table 2 in the Acceptance criteria section to list the limits for specified impurities, any unspecified impurity, and total impurities.

   • Delete the Note "Disregard any peak that is less than 0.05%" under the Analysis section and add a Note of "A reporting threshold of 0.05% may be suitable when the maximum daily dose is ≤2 g" under the Acceptance criteria section, with a reference to User-Determined Reporting Thresholds 〈477〉 for user flexibility.

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

 (SM2: S. Parepalli)

 Case ID—SUB-528