Rapamycin;
(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26, 27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]-oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone [53123-88-9]
BRIEFING
Sirolimus. Because there is no existing USP monograph for this drug substance, a new monograph is being proposed. On the basis of comments received, the proposal previously published in PF 47(1) [Jan.–Feb. 2021] was canceled and is replaced with this new proposal based on the following validated methods of analysis.
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The liquid chromatographic procedure in the Assay is based on analyses performed with the Zorbax Eclipse XDB-C8 brand of column with L7 packing. The typical retention time for sirolimus is about 10 min.
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The liquid chromatographic procedure in the test for Organic Impurities is based on analyses performed with the Zorbax Eclipse Plus C18 brand of column with L1 packing. The Zorbax Eclipse XDB-C18 brand of column with L1 packing is also suitable. The typical retention time for sirolimus is about 16 min. In a change from the PF 47(1) proposal, quantitation is now performed using area-normalization and the acceptance criteria for any individual unspecified impurity is widened from 0.10% to 0.15%.
Description and solubility information: White to off-white powder. Freely soluble in chloroform, in acetone, and in acetonitrile. Insoluble in water.
(SM1: M. Puderbaugh)
Correspondence Number—C151981