1-Butanol, 2,2′-(1,2-ethanediyldiimino)bis-, dihydrochloride, [S-(R*,R*)]-;
(+)-2,2′-(Ethylenediimino)-di-1-butanol dihydrochloride;
(2S,2′S)-2,2′-[Ethane-1,2-diylbis(azanediyl)]dibutan-1-ol dihydrochloride [1070-11-7]
BRIEFING
Ethambutol Hydrochloride. This proposal is based on the version of the monograph official as of August 1, 2020. It is proposed to revise the monograph with the following changes:
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Update the chemical name of Ethambutol Hydrochloride to include "dihydrochloride" in the Chemical Information section to be consistent with current USP naming conventions.
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Update the upper limit of the Acceptance criteria in the Definitionand in the Assay from NMT 100.5% to NMT 102.0%.
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In the test for Identification:
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Rename Identification B as Identification C, and add a new Identification B based on retention time agreement, as obtained in the proposed Assay.
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Add Ethambutol Hydrochloride to the Sample solution under Identification C for clarity.
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Replace the titration-based test with an HPLC-based procedure in the Assay by using derivatization techniques. The liquid chromatographic procedure was validated using the Hypersil BDS brand of column with L1 packing. The typical retention time for derivatized ethambutol is about 15 min.
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In the test of Organic Impurities:
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Delete Solution A, Solution B, Mobile phase, and the Chromatographic system, as these are referenced in the Assay.
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Add the Sensitivity solution to support the addition of the Signal-to-noise ratio requirement under the System suitability requirement.
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Update the term "ethambutol" to "derivatized ethambutol" in the rU and rS definitions within the calculation section, as the API undergoes derivatization during both standard and sample preparation.
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Add Table 2 and a Note to the System suitability section to present relative retention times as an aid in peak assignment.
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Update Table 3 in the Acceptance criteria section to list the limits for specified impurities, any unspecified impurity, and total impurities.
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In the test of Limit of Aminobutanol add "in water" for the Standard solution and Sample solution for clarity.
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Update the USP Reference Standards 〈11〉 section to include the chemical name for USP Aminobutanol RS.
Additionally, minor editorial changes have been made to update the monograph to current USP style.
(SM1: S. Parepalli)
Case ID—SUB-499
USP REFERENCE STANDARDS FOR PURCHASE
USP Aminobutanol RSUSP Ethambutol Hydrochloride RS
USP Ethambutol Related Compound A RS
USP Ethambutol Related Compound B RS