Morphinan-6-one, 17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxy-, hydrochloride, (5α)-;
17-(Cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxy morphinan-6-one hydrochloride
17-Cyclopropylmethyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride
[16676-29-2] Free base
C20H23NO4 341.41
[16590-41-3] Dihydrate C20H23NO4·HCl·2H2O 413.89413.90
[850808-02-5]
BRIEFING
Naltrexone Hydrochloride. This proposal is based on the version of the monograph official as of May 1, 2020. On the basis of comments received, it is being proposed to revise the monograph with the following changes:
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Update the chemical name of naltrexone hydrochloride in the Chemical Information section to be consistent with the USP naming convention.
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Update the molecular weights of naltrexone hydrochloride and its dihydrate form in the Chemical Information section.
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In the Assay:
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Revise the concentrations of the Standard solution, System suitability solution, and Sample solution based on the supporting data.
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Add a Column temperature under the chromatographic conditions based on the supporting data.
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Update the molecular weight of naltrexone hydrochloride in the calculation.
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In the Organic Impurities test:
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Revise the concentration of the Sensitivity solution based on the supporting data.
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Add a table and a Note in the System suitability section to present the relative retention times as an aid in peak assignment.
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Add the relative retention times for the three newly identified impurities, N-formyl noroxymorphone, bisnaltrexone aldol, and O-cyclopropylmethyl naltrexone, and update the relative retention times of the existing impurities based on the supporting data.
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Revise the calculation equation to include molecular weight conversion.
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Revise the Acceptance criteria section to include a reference to User-Determined Reporting Thresholds 〈477〉 for user flexibility.
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Update Table 3 in the Acceptance criteria to list the limits for specified impurities, any unspecified impurity, and total impurities. In addition, propose the inclusion of acceptance criteria limits for two newly identified impurities, N-formyl noroxymorphone and O-cyclopropylmethyl naltrexone, revise the relative response factors for the other five impurities, and update the limit for any unspecified impurity in Table 3 based on the supporting data.
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Revise the Packaging and Storage section to include a temperature requirement.
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Update the molecular weight for USP Naltrexone Related Compound A RS in the USP Reference Standards section.
Additionally, minor editorial changes have been made to update the monograph to current USP style.
(SM2: S. Parepalli)
Case ID-SUB-2979