10H-Phenothiazine-10-propanamine, 2-chloro-N,N-dimethyl-, monohydrochloride;
2-Chloro-10-[3-(dimethylamino)propyl]phenothiazine monohydrochloride [69-09-0]
BRIEFING
Chlorpromazine Hydrochloride. 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:
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Add an image and update the molecular weight in the Chemical Information section.
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Revise Identification A to allow the flexibility of using either 197A or 197K.
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Revise Identification B to be based on retention time agreement from the proposed Assay instead of from the TLC test for Other Alkylated Phenothiazines.
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Revise Identification C to allow flexibility.
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Replace the titration-based Assay with a more specific LC procedure. The procedure was validated using the Venusil ASB C8 brand of column with L7 packing. The typical retention time for chlorpromazine is about 11 min.
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Update the Definition and Acceptance criteria in the Assay to align with typical LC instrument performance.
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Delete the TLC-based test for Other Alkylated Phenothiazines.
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Add a validated LC procedure for the Organic Impurities test. The procedure was validated using the Venusil ASB C8 brand of column with L7 packing. The typical retention time for chlorpromazine is about 11 min.
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Remove the nonspecific test for Melting Range or Temperature 〈741〉 as the other tests in the monograph can adequately monitor the quality of the drug substance.
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Update the requirement in the Packaging and Storage section.
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Add USP Bromopromazine RS, USP Chlorpromazine Related Compound A RS, USP Chlorpromazine Related Compound D RS, and USP Promazine Hydrochloride RS to the USP Reference Standards section to support the proposed Organic Impurities test.
Additionally, minor editorial changes have been made to update the monograph to current USP style.
(SM4: Y. Yang)
Case ID—SUB-2073