1,4-Butanediol, dimethanesulfonate;
1,4-Butanediol dimethanesulfonateButane-1,4-diyl dimethanesulfonate [55-98-1]
BRIEFING
Busulfan. This proposal is based on the version of the monograph official prior to 2013. On the basis of comments received, the previous proposal which appeared in PF 45(5) was canceled and is being replaced with the following proposal. It is proposed to revise the monograph with the following changes:
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Update the molecular weight and chemical name of busulfan in the Chemical Information section.
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Revise the Definition as follows:
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Revise the Acceptance criteria from 98.0%–100.5% to 98.0%–102.0%, based on available FDA-approved specifications.
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Add a Caution statement based on the safety requirements for handling busulfan.
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Revise the Identification section as follows:
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Replace the use of wet chemistry in Identification A with Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or 197K.
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Replace the use of wet chemistry in Identification B with the chromatographic retention time agreement using the proposed Assay.
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Delete Identification C as the test is non-specific. The remaining Identification tests are sufficient.
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Replace the titration procedure in the Assay with a gas chromatography (GC) procedure validated using the DB-5 brand of column with phase G27. The typical retention time for busulfan is about 13 min.
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Add the test for Organic Impurities using the same GC procedure as in the Assay. The typical retention time for busulfan is about 13 min.
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Add the test for the Limit of Methanesulfonic Acid. The ion chromatography (IC) procedure was validated using the Dionex Ion Pac AG11-HC brand of guard column with L61 packing and the Dionex Ion Pac AS11-HC brand of analytical column with L81 packing. The typical retention time for methanesulfonate is about 12 min.
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Delete the test for Melting Range or Temperature. The proposed tests for Organic Impurities and the Limit of Methanesulfonic Acid can adequately monitor the quality of the drug substance.
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Add a storage condition to the Packaging and Storage section.
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Add a USP Reference Standards section to include USP Busulfan RS and USP Potassium Methanesulfonate RS to support the monograph revisions.
Additionally, minor editorial changes have been made to update the monograph to current USP style.
(SM3: A. Leeks, Jr)
Case ID—SUB-1676, SUB-2360, SUB-2361, SUB-2363