l-Proline, 1-[(2S)-3-mercapto-2-methyl-1-oxopropyl]-;
1-[(2S)-3-Mercapto-2-methylpropionyl]-l-proline;
[(S)-3-Mercapto-2-methylpropanoyl]-l-proline [62571-86-2]
BRIEFING
Captopril. This proposal is based on the version of the monograph official as of December 1, 2021. It is proposed to revise the monograph with the following changes:
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Add an additional chemical name and update the molecular weight in the Chemical Information section to be consistent with the current chemical information.
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Revise Identification A to allow the flexibility of using either 〈197A〉 or 〈197K〉.
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Add Identification B based on retention time agreement, as obtained in the proposed Assay.
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Replace the titration procedure in the Assay with a liquid chromatographic procedure similar to the Organic Impurities test, based on the validation performed using a Microbondapak C18 brand of column with L1 packing. The typical retention time for captopril is about 6 min.
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In the test for Organic Impurities:
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Update the Mobile phase preparation to provide additional clarification.
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Update the preparation of the System suitability solution to provide flexibility.
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Update the HPLC column particle size.
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Add an Autosampler temperature and Run time in the Chromatographic system section based on available data.
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Add a table and Note in the System suitability section to present relative retention times as an aid in peak assignment.
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Update the quantitation to calculating the content against USP Captopril Disulfide RS.
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Update the acceptance criteria for any unspecified impurity in Table 2 to 0.10% based on the International Council for Harmonisation (ICH) Q3A guideline for drug substances with a maximum daily dose of <2 g/day. Manufacturers are encouraged to submit their FDA-approved specifications, if different. The Standard solution is updated to the same concentration as per the expectations of the Expert Committee.
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Clarify that Total impurities excludes captopril disulfide.
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Add Relative standard deviation and Signal-to-noise ratio requirements to the System suitability section to strengthen the method. A Sensitivity solution is also added to support the additional requirement.
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Add a reporting threshold to the Acceptance criteria. The proposed reporting threshold corresponds to that of the ICH guideline for drug substances with a maximum daily dose of <2 g/day. Manufacturers are encouraged to submit their FDA-approved level(s), if different.
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Additionally, minor editorial changes have been made to update the monograph to current USP style.
(SM2: S. Shane)
Case ID—SUB-842