Pyrrolidinium, 3-[(SR)-(cyclopentylhydroxyphenylacetyl)oxy]-1,1-dimethyl-, [RS-] bromide;
(RS)-[3-(SR)-Hydroxy-1,1-dimethylpyrrolidinium bromide] α-cyclopentylmandelate [51186-83-5]
BRIEFING
Glycopyrrolate. 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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Update the Chemical Information section with a modified structure for better clarity and to include the UNII code for glycopyrrolate.
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Revise the test for Organic Impurities, Procedure 1 as follows:
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Add a Sensitivity solution containing glycopyrrolate related compound A in the Suitability requirements and propose a Signal-to-noise requirement.
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Remove the Tailing factor requirement under the System suitability section since the procedure is well supported by other suitability tests.
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In the Acceptance criteria, add a reference to User-Determined Reporting Thresholds 〈477〉 for user flexibility. Revise the table to list only the limits for specified, unspecified, and total impurities.
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Add Table 2 and a Note in the System suitability section to present relative retention times as an aid in the peak assignment.
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The acceptance criterion for glycopyrrolate related compound A is tightened from 0.15% (w/w) to 0.016% (w/w) to align with International Council for Harmonisation (ICH) M7 guidelines since this impurity is a potential mutagenic impurity.
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Revise the test for Organic Impurities, Procedure 2 as follows:
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Add an equilibration step in Table 4 and delete the statement "Return to original conditions and equilibrate the system."
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Remove the Tailing factor and add a Relative standard deviaton requirement under the System suitability section.
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In the Acceptance criteria, add a reference to User-Determined Reporting Thresholds 〈477〉 for user flexibility. Revise the table to list only the limits for specified, unspecified, and total impurities.
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Add Table 5 and a Note in the System suitability section to present relative retention times as an aid in the peak assignment.
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Revise the test for Limit of Erythro Isomer as follows:
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Remove the Tailing factor requirement because there are sufficient system suitability tests for the procedure.
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Add a Note in the System suitability section to present relative retention times as an aid in the peak assignment. Remove the table in the Acceptance criteria and list the limit of glycopyrrolate erythro isomer.
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Additionally, minor editorial changes have been made to update the monograph to current USP style.
(SM3: M. Jonnada)
Case ID—SUB-613