BRIEFING

 Hydrocodone Bitartrate. This proposal is based on the version of the monograph official as of May 1, 2020. On the basis of comments received, the previous proposal that appeared in PF 39(3) [May–Jun. 2013] has been canceled and is replaced with the following proposal. It is proposed to revise the monograph with the following changes:

1. Remove an outdated CAS number and the anhydrous form of hydrocodone bitartrate from the chemical information of Hydrocodone Bitartrate. The anhydrous form of hydrocodone bitartrate is not referenced in any approved drug product currently on the market.

2. Revise the Definition and the Acceptance criteria in the Assay to be consistent with the current practice.

3. Revise Identification A to allow flexibility for the use of 197A, 197K, or 197M.

4. Replace the UV spectroscopic procedure in Identification B with the chromatographic retention time agreement as obtained in the proposed Assay.

5. Add the Organic Impurities test and replace the liquid chromatography (LC) procedure in the Assay with an LC procedure which uses the same chromatographic conditions as in the proposed Organic Impurities test. The proposed procedures in both the Assay and the Organic Impurities test were validated using the ACQUITY UPLC BEH C18 brand of column with L1 packing. The typical retention time for hydrocodone is about 6 min.

6. Remove the Chloride test, as the remaining tests, including the proposed Organic Impurities test, are sufficient for this drug substance monograph as a public standard.

7. Clarify the procedure in the Loss on Drying test.

8. Add the storage temperature requirement to the Packaging and Storage section based on the approved manufacturer's storage conditions.

9. Update the USP Reference Standards section to remove USP Dihydrocodeine Bitartrate RS and to include USP Oxycodone Related Compound C RS.

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

 (SM2: W. Yang)

 Correspondence Number—C187477