BRIEFING

 N-Acetyl-dl-tryptophan. This proposal is based on the version of the monograph official as of April 1, 2026. On the basis of comments and data received, it is being proposed to make the following changes:

1. Revise the acceptance criteria in the Definition and Assay from NLT 99.0% and NMT 101.0% to NLT 98.0% and NMT 102.0%. This change is justified because the Assay procedure has been updated from a nonspecific method to a specific HPLC method using external calibration, which provides improved analyte specificity and supports a wider acceptance range.

2. Replace the titrimetric method in the Assay with an HPLC method. The proposed HPLC method in the Assay is the same method used for the Organic Impurities test. It is based on the analyses performed using the Nucleosil 100-5 C18 brand of column with L1 packing. The typical retention times for N-acetyl-dl-tryptophan and tryptophan related compound A are about 31.0 and 34.4 min, respectively.

3. Revise the Iron test by updating the Sample solution to increase the volume of hydrochloric acid from 50 to 80 mL and heating temperature from 50° to 80° to account for sample solubility and dissolution.

4. Add drying time in the Loss on Drying test.

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

 (EXC1: S. Saladi)

 Case ID—SUB-1061, SUB-3167