BRIEFING

 Fluoxetine Hydrochloride. 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 46(5) [Sep.–Oct. 2020] was canceled and it is proposed to revise the monograph with the following changes:

1. Revise Identification A to allow the use of 197A or 197K.

2. Replace the liquid chromatographic procedures in the Assay and the test for Organic Impurities with a procedure that does not require the use of stabilizer-free tetrahydrofuran and is more specific. This procedure was validated using the XSelect CSH Fluoro-Phenyl brand of column with L43 packing. The typical retention time for fluoxetine is about 36 min.

3. In the Acceptance criteria of the Organic Impurities test, the numerical reporting threshold has been replaced with a reference to User-Determined Reporting Thresholds 〈477〉 for user flexibility. For more information about this change, please see the USP Compendial Notice "New Chapter 〈477〉 User-Determined Reporting Thresholds and its Implementation in USP–NF Monographs".

4. Add a test for Residue on Ignition for consistency with approved applications. Specify to use a platinum crucible due to the fluorine content of the molecule.

5. Remove USP Fluoxetine Related Compound B RS from the USP Reference Standards section to align with the Reference Standards used in the proposed Assay and Organic Impurities test.

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

 Manufacturers are encouraged to submit their FDA-approved specifications to USP if they are different from those proposed.

 (SM4: S. Dragan)

 Case ID—SUB-441