BRIEFING

 Ampicillin. This proposal is based on the version of the monograph official as of April 1, 2021. On the basis of comments received, it is proposed to make the following changes:

1. Update the chemical information of ampicillin trihydrate.

2. Revise Identification A for clarification and to allow the flexibility of using 197A or 197K.

3. Add Identification B based on retention time agreement, as obtained in the Assay.

4. In the Assay, revise the System suitability solution, Standard solution, and Sample solution based on the validated method. Add the relative retention times in the System suitability section to aid in peak assignment.

5. In the sentence right under Organic Impurities, Procedure 1, change “ampicillin thiazepine” to “ampicillin thiazepine analog”.

6. In Organic Impurities, Procedure 1, revise the Standard stock solution, Standard solution, and Sensitivity solution based on the validated method. Revise the Relative standard deviation in the Suitability requirements section based on method validation.

7. In Organic Impurities, Procedure 3, add a Sensitivity solution and Signal-to-noise ratio for System suitability.

8. In Organic Impurities, Procedure 4, add Relative standard deviation, Sensitivity solution, and Signal-to-noise ratio for System suitability. Revise the Acceptance criteria for clarification.

9. In each of Organic Impurities, Procedure 1, Organic Impurities, Procedure 3, and Organic Impurities, Procedure 4, add a table and Note in the System suitability section to present relative retention times as an aid in peak assignment. The relative retention time of amoxicillin is added to Table 2 in Organic Impurities, Procedure 1. Revise the tables in the Acceptance criteria sections to list only the limits for specified impurities, any unspecified impurity, and total impurities. The chemical name of amoxicillin related compound A is removed from the footnote since it is listed in the USP Reference Standards section.

10. In the Bacterial Endotoxins Test, revise the requirement for clarification and remove the numerical limit, and instead refer to Bacterial Endotoxins Test 〈85〉 for the determination of limits.

11. In the USP Reference Standards section, update the molecular weight of diphenyldiketopiperazine in USP Ampicillin System Suitability Mixture RS.

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

 (SM1: F. Gu)

 Case ID—SUB-1376