1H-Indole-5-sulfonic acid,2-(1,3-dihydro-3-oxo-5-sulfo-2H-indol-2-ylidene)-2,3-dihydro-3-oxo-, disodium saltsodium salt (1:2);
Disodium 3,3′-dioxo-[Δ2,2'-biindoline]-5,5′-disulfonate [860-22-0]
BRIEFING
Indigotindisulfonate Sodium. This proposal is based on the version of the monograph official as of June 1, 2023. It is proposed to revise the monograph with the following changes:
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Update the chemical name of indigotindisulfonate sodium in the Chemical Information section.
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Revise the Definition from NLT 96.0% and NMT 102.0% on the dried basis to NLT 97.5% and NMT 102.0% on the anhydrous basis based on approved specification. The Acceptance criteria in the Assay are also updated accordingly.
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Replace four Identification tests with three Identification tests to more closely align with approved specifications.
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Replace the UV-based Assay with a validated LC procedure sharing the same Mobile phase and Chromatographic system as in the proposed Organic Impurities procedure. Both procedures were validated using the Poroshell 120 SB-C8 brand of column with L7 packing. The typical retention time for indigotindisulfonate is about 43 min.
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Remove the tests for Arsenic 〈211〉 and Lead 〈251〉 from this monograph since these elemental impurities will be controlled in the drug product using the risk-based approach specified in Elemental Impurities—Limits 〈232〉. The risk-based approach will be used to determine the presence of an elemental impurity (in components of the formulation or in the drug product) and the appropriate level of control. Therefore, it is redundant to include these tests in this monograph.
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Replace the Loss on Drying 〈731〉 test with the Water Determination 〈921〉 test to align with approved specifications.
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Add requirements for Bacterial Endotoxins Test 〈85〉, Microbial Enumeration Tests 〈61〉, and Tests for Specified Microorganisms 〈62〉 based on approved specifications.
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Remove the nonspecific Sulfur Content and Water-Insoluble Substances tests because other tests in the monograph can adequately monitor the quality of the drug substance.
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Update the requirements in the Packaging and Storage section.
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Add a Labeling requirement for parenteral applications.
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Add USP Indigotindisulfonate Sodium System Suitability Mixture RS to the USP Reference Standards section to support the proposed test for Organic Impurities.
Additionally, minor editorial changes have been made to update the monograph to current USP style.
This proposal has undergone the prospective harmonization process with the European Pharmacopoeia.
(SM4: Y. Yang)
Case ID—SUB-1389
USP REFERENCE STANDARDS FOR PURCHASE
USP Indigotindisulfonate Sodium RSUSP Indigotindisulfonate Sodium System Suitability Mixture RS