BRIEFING

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

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

2. Replace Identification B based on the UV absorptivities with the retention time agreement of the isoproterenol peak of the Standard solution and the Sample solution from the proposed Assay.

3. Add Identification C for the chloride counter ion.

4. Delete the procedure for Content of Chloride, as the counter ion test is not necessary for this drug substance monograph.

5. Replace the current liquid chromatographic procedure in the Assay, which uses time-consuming freshly prepared reagents and an outdated chromatographic column, with a validated liquid chromatographic procedure that is based on analyses performed using the Inert Sustain Swift C18 brand of column with L1 packing. The typical retention time for isoproterenol is about 7 min.

6. Add an Organic Impurities test based on a validated HPLC procedure. The proposed liquid chromatographic procedure is based on analyses performed using the Lichrosphere RP18 brand of column with L1 packing. The typical retention time for isoproterenol is about 3 min.

7. Delete the Limit of Isoproterenone test, as the proposed Organic Impurities test can be used to quantify isoproterenol related compound A, also known as isoproterenone.

8. Delete the nonspecific Melting Range or Temperature test because all the other tests in the monograph can adequately monitor the quality of the drug substance.

9. Update the storage conditions in the Packaging and Storage section.

10. Add USP Isoproterenol Related Compound A RS and USP Metaproterenol Sulfate RS to the USP Reference Standards section to support the proposed revisions.

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

 Description and solubility information: A white to almost white crystalline powder. Freely soluble in water; sparingly soluble in ethanol; practically insoluble in methylene chloride, in chloroform, and in ether.

 (SM5: P. Jagu)

 Correspondence Number—C246035