BRIEFING

 Citalopram Tablets. This proposal is based on the version of the monograph official as of May 1, 2020. The following revisions are proposed:

1. Replace Identification A with a test based on the UV spectrum agreement of the major peak in the Assay to eliminate the use of hazardous solvents. Accordingly, add the use of a diode array detector in the Chromatographic system of the Assay.

2. The chromatographic procedure in the Assay was validated using the Spherisorb ODS1 brand of column with L1 packing to remove the use of an Internal standard solution for quantitation. The typical retention time for citalopram is about 5.8 min. Accordingly, the following revisions are proposed:

   • Add a System suitability solution containing USP Citalopram Related Compound C RS and USP Citalopram Hydrobromide RS, and revise the Resolution requirement to be based on the peaks of these compounds, as they are a critical pair.

   • Revise the Sample solution as per the method validation and to align with current USP style.

   • Revise the Detector from 254 nm to 240 nm based on validation data indicating the latter is the maximum absorbance wavelength for the citalopram peak, and add a Run time for the isocratic procedure in the Chromatographic system.

   • Remove the Column efficiency and add a Tailing factor requirement in the Suitability requirements to be consistent with Chromatography 〈621〉, System Suitability. Additionally, revise the Relative standard deviation criterion based on the validation data.

   • In the Analysis, replace the equation based on the use of an Internal standard solution with an equation consistent with an external Standard solution quantitation approach.

3. Revise portions of the chromatographic procedure in the Organic Impurities test to align with current expectations. The following revisions are proposed based on laboratory data, as needed:

   • Revise the System suitability solution to remove USP Citalopram Related Compound A RS and USP Citalopram Related Compound B RS because both are no longer needed to monitor resolution or for quantitation purposes. USP Citalopram Related Compound E RS is maintained to serve as a retention time marker because the relative retention time was reported to shift.

   • Revise the concentrations of the Standard solution and Sensitivity solution to align with the existing unspecified degradation impurity limit and the expected reporting threshold, respectively.

   • Add a Run time for the isocratic procedure in the Chromatographic system.

   • Revise the Resolution criterion from NLT 3 to NLT 2.0 in the Suitability requirements, which ensures baseline separation of the critical pair. Additionally, revise the Signal-to-noise ratio criterion appropriately for the proposed Sensitivity solution.

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

   • Revise the table in the Acceptance criteria to list limits for specified degradation products, any unspecified degradation product, and total degradation products to align with the International Council for Harmonisation Q3B guidelines. The relative response factors are also listed in this table.

   • Revise the Acceptance criteria to add a reference to User-Determined Reporting Thresholds 〈477〉 for user flexibility. For more information about this change, please see the USP Compendial Notice “New Chapter 〈477〉 User-Determined Reporting Thresholds and its Implementation in USP–NF Monographs”.

4. Remove USP Citalopram Related Compound A RS, USP Citalopram Related Compound B RS, and USP Citalopram Related Compound F RS from the USP Reference Standards section because the uses are proposed to be eliminated in the Organic Impurities and Assay procedures.

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

 (SM4: T. Bililign)

 Case ID—SUB-231