BRIEFING

 Nefazodone Hydrochloride. This proposal is based on the version of the monograph official as of May 1, 2021. A revision to the Assay and Organic Impurities test to replace USP Nefazodone Related Compound A RS with USP Trazodone Related Compound F RS in the preparation of the System suitability solution is necessary to ensure continuity of supply of the reference material. These reference standards are identical with respect to structure and chemical name. The revision eliminates a redundant reference material from the USP Reference Standards catalog. The following changes to the monograph are also proposed:

1. Update the chemical name of nefazodone hydrochloride in the Chemical Information section to be consistent with current USP naming conventions.

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

3. Revise the Assay as follows:

   • Remove the instruction to degas Solution A and Solution B, as this is understood to be a routine laboratory practice.

   • Update the text in the Resolution, under Suitability requirements, to be consistent with the elution order of the impurity peaks.

4. Revise the test for Organic Impurities as follows:

   • Add a Sensitivity solution to support a new Signal-to-noise ratio requirement to verify adequate chromatographic system sensitivity.

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

   • Update the text in the Resolution, under Suitability requirements, to be consistent with the elution order of the impurity peaks.

   • Add Relative standard deviation for nefazodone under the System suitability requirements.

   • Revise Table 3 in the Acceptance criteria to list only the limits for specified impurities, any unspecified impurity, and total impurities.

   • Under the Acceptance criteria, add a reference to User-Determined Reporting Thresholds 〈477〉 for user flexibility.

5. Update the USP Reference Standards section to reflect current chemical information.

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

 The comment period for this revision ends on July 31, 2025. In the absence of any significant adverse comment, it is proposed to implement this revision via an Interim Revision Announcement with an official date of November 1, 2025.

 (SM4: R. Radhakrishnan)

 Case ID—SUB-1854