BRIEFING

 Carbidopa. This proposal is based on the version of the monograph official as of May 1, 2020. It is proposed to revise the monograph with the following changes:

1. Update the Chemical Information section to reflect the molecular weight and chemical name as per the current USP Dictionary of USAN and International Drug Names.

2. Update the Definition to express carbidopa content on the dried basis.

3. Revise Identification A to allow the flexibility of using either 197A or 197M.

4. Replace the Assay procedure to be consistent with the proposed Organic Impurities test.

5. Add a new Limit of p-Toluenesulfonic Acid test. The liquid chromatographic procedure was validated using the XTerra RP18 brand of column with L1 packing. The typical retention time for carbidopa is about 4 min.

6. Delete the Limit of Methyldopa and Carbidopa Related Compound A test and add a new general Organic Impurities test procedure that is suitable for these impurities. The liquid chromatographic procedure was validated using the XBridge C18 brand of column with L1 packing. The typical retention time for carbidopa is about 3 min.

7. Tighten the limit of methyldopa and carbidopa related compound A in the proposed new Organic Impurities test based on FDA-approved specifications.

8. Simplify the Sample solution preparation and add an Analysis section to calculate the concentration of Carbidopa as the monohydrate in the Sample solution under the Optical Rotation test.

9. Update the Packaging and Storage section to include the storage temperature.

 The current Loss on Drying test includes limits appropriate for the monohydrate form of carbidopa. Manufacturers with FDA-approved drug products using the anhydrous form of carbidopa are encouraged to submit their Loss on Drying specifications for consideration in a future revision.

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

 (SM4: D. Singh)

 Case ID—SUB-998