BRIEFING

 Norepinephrine Bitartrate. This proposal is based on the version of the monograph official as of Jan. 1, 2021. It is proposed to make the following changes:

1. Update the chemical name in the chemical information section to be consistent with the current USP naming convention. Remove the anhydrous form in the chemical information section to be consistent with package inserts for approved products.

2. Add 197A as an alternate test method for Identification A to allow flexibility to users.

3. Replace the colorimetric test in Identification B with a chromatographic test, based on the retention time agreement as obtained in the proposed Assay.

4. Delete the colorimetric test in Identification C as the proposed Identification A and Identification B can adequately establish the identity of the drug substance.

5. Replace the titration-based Assay procedure with an HPLC procedure. The liquid chromatographic procedure is validated using the Chromolith Performance RP-18e brand of column with L1 packing. The typical retention time for norepinephrine is about 4.3 min.

6. Replace the UV absorption based Limit of Arterenone test with an HPLC based Organic Impurities test. The liquid chromatographic procedure is validated using the Chromolith Performance RP-18e brand of column with L1 packing. The typical retention time for norepinephrine is about 4.3 min.

7. Delete the sample size in the test for Residue on Ignition and default to the sample requirements in the general chapter Residue on Ignition 〈281〉 to be consistent with the FDA-approved application.

8. Add USP Norepinephrine Related Compound D RS and USP Norepinephrine Related Compound E RS to the USP Reference Standards section to support the proposed procedures.

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

 (SM2: F. Gu)

 Correspondence Number—C211066