Piperazine, 1-[4-[[2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-4-(1-methylethyl)-, cis-.
cis-1-[p-[[2-(2,4-Dichlorophenyl)-2-(l1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-4-isopropylpiperazine
1-[4-{[(2RS,4SR)-2-[(1H-1,2,4-Triazol-1-yl)methyl]-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl]methoxy}phenyl]-4-isopropylpiperazine [67915-31-5]
BRIEFING
Terconazole. 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 name and molecular weight and add the IUPAC name 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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Add Identification B based on retention time agreement as obtained in the Assay.
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Replace the titration-based Assay and update the Organic Impurities test with a validated liquid chromatographic procedure, sharing the same Chromatographic system and Mobile phase. The liquid chromatographic procedure was validated using the X-Bridge BEH Shield brand of column with L1 packing. The typical retention time for terconazole is about 12 min.
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Revise the test for Organic Impurities as follows:
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Revise the note about protecting solutions from light in the test.
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Revise the Column particle size from 3.0-µm to 3.5-µm as per updated validation method.
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Revise the concentration of the Standard solution to reflect the limit of any unspecified impurity.
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Add the Sensitivity solution to support the addition of the Signal-to-noise ratio requirement.
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Delete the Tailing factor requirement as the other Suitability requirements are sufficient.
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Add a table and a note to the System suitability to present relative retention times as an aid in peak assignment. Revise the table in the Acceptance criteria to list only the limits for specified impurities, any unspecified impurity, and total impurities.
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Revise the relative response factor for terconazole regioisomer from 0.94 to 0.99 to align with the updated Organic Impurities test.
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Update the trivial and IUPAC names of terconazole regioisomer and terconazole diastereomer in Table 3 and Table 4 to be consistent with USP style.
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In the Acceptance criteria, the disregard limit (numerical reporting threshold) has been replaced with a reference to User-Determined Reporting Thresholds 〈477〉 for user flexibility. For more information about this change, please see the USP Compendial Notice “New Chapter 〈477〉 User-Determined Reporting Thresholds and its Implementation in USP–NF Monographs”.
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Additionally, minor editorial changes have been made to update the monograph to current USP style.
(SM1: S. Parepalli)
Case ID—SUB-281