BRIEFING

 Neostigmine Methylsulfate Injection. This proposal is based on the version of the monograph official prior to 2013. It is proposed to revise the monograph with the following changes:

1. Replace the colorimetry-based Identification with Identification A based on the retention time agreement as obtained in the proposed Assay.

2. Add Identification B based on the UV spectrum agreement as obtained in the proposed Assay.

3. Replace the nonspecific spectrophotometry-based Assay procedure with a validated liquid chromatographic procedure, which is based on validation performed with the Kinetex C8 brand of column with L7 packing. The typical retention time for neostigmine is about 20 min.

4. Add an Organic Impurities test to strengthen the quality standard for this drug product. The proposed liquid chromatographic procedure is similar to the proposed Assay.

5. Delete the Other Requirements section as the reference to Injections and Implanted Drug Products 〈1〉, and add the Bacterial Endotoxins Test, Particulate Matter in Injections, Sterility Tests, and Container Content for Injections tests to the Specific Tests section based on FDA-approved specifications.

6. Add the storage temperature in the Packaging and Storage section, to be consistent with manufacturer's storage conditions.

7. Add USP Neostigmine Related Compound A RS, USP Neostigmine Related Compound B RS, and USP Neostigmine Related Compound C RS to the USP Reference Standards section to support the proposed Assay and test for Organic Impurities.

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

 (SM4: D. Singh)

 Correspondence Number—C225414