BRIEFING

 Nefazodone Hydrochloride Tablets. This proposal is based on the version of the monograph official as of May 1, 2020. A revision to the 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. Replace the IR spectral agreement test in Identification A with a test based on UV spectral agreement using the proposed Assay.

2. Revise the Assay as follows:

   • Remove the instruction to filter and degas the Mobile phase, as this is understood to be a routine laboratory practice.

   • Revise the Detector in the Chromatographic system to support the proposed Identification A.

   • Update the Chromatographic system to include Run time.

   • Revise the Relative standard deviation requirement in the System suitability based on the supporting data.

3. Revise the test for Organic Impurities as follows:

   • Revise the concentration of the Standard solution to align with the limit of any unspecified degradation product.

   • Add a Sensitivity solution to determine the Signal-to-noise ratio under the Suitability requirements.

   • Update the Chromatographic system to include a Run time based on the supporting data.

   • Add Table 1 and update the Note in the System suitability section to present relative retention times as an aid in peak assignment.

   • Add a Relative standard deviation for nefazodone in the Suitability requirements, based on the supporting data, to align with the change in the Standard solution concentration.

   • Revise Table 2 in the Acceptance criteria to list only the limits for specified degradation products, any unspecified degradation product, and total degradation products.

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

4. Update the USP Reference Standards section to be consistent with 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-1855