(eye'' da roo' bi sin hye'' droe klor' ide).
5,12-Naphthacenedione, 9-acetyl-7-[(3-amino-2,3,6-trideoxy--l-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,9,11-trihydroxyhydrochloride, (7S-cis)-.
(1S,3S)-3-Acetyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-6,11-dioxo-1-naphthacenyl 3-amino-2,3,6-trideoxy--l-lyxo-hexopyranoside, hydrochloride [57852-57-0].
» Idarubicin Hydrochloride contains not less than 960 µg and not more than 1030 µg of C26H27NO9·HCl per mg, calculated on the anhydrous basis.
[CautionGreat care should be taken to prevent inhaling particles of Idarubicin Hydrochloride and exposing the skin to it. ]
Packaging and storage Preserve in tight containers.
Labeling The amorphous form is so labeled.
USP Reference standards 11
Crystallinity 695: meets the requirements, except where it is labeled as amorphous, most of the particles do not exhibit birefringence and extinction positions.
pH 791: between 5.0 and 6.5, in a solution containing 5 mg per mL.
Water, Method I 921: not more than 5.0%.
Chromatographic purity Using the chromatogram of the Assay preparation obtained in the Assay, and disregarding the solvent peak, calculate the percentage of each impurity taken by the formula:
100rI / rSin which ri is the response of each impurity peak; and rS is the sum of the responses of all the peaks: not more than 1.0% of any individual impurity is found; and the sum of all impurities is not more than 3.0%.
Mobile phase Prepare a mixture of water, acetonitrile, methanol, and phosphoric acid (540:290:170:2). Dissolve 1 g of sodium lauryl sulfate in 1000 mL of this solution, adjust with 2 N sodium hydroxide to a pH of 3.6 ± 0.1, pass through a filter having a porosity of 0.5 µm or finer, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent Prepare as directed for Mobile phase, except to omit the sodium lauryl sulfate.
Standard preparation Dissolve an accurately weighed quantity of USP Idarubicin Hydrochloride RS in Diluent to obtain a solution having a known concentration of about 500 µg of idarubicin hydrochloride per mL.
Assay preparation Transfer about 50 mg of Idarubicin Hydrochloride, accurately weighed, to a 100-mL volumetric flask, dissolve in Diluent, dilute with Diluent to volume, and mix.
Resolution solution Prepare an aqueous solution containing 1 mg of Idarubicin Hydrochloride per mL. To 2 mL of this solution in a test tube, add 20 µL of hydrochloric acid, and heat in an oil bath at 95 for about 8 minutes. Mix 1 mL of this solution and 9 mL of Diluent. This Resolution solution contains a mixture of 4-demethoxydaunorubicinone and idarubicin.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains packing L13. The flow rate is about 2 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.5 for 4-demethoxydaunorubicinone and 1.0 for idarubicin; and the resolution, R, between the 4-demethoxydaunorubicinone peak and the idarubicin peak is not less than 9.5. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the capacity factor, k¢, for the idarubicin peak is not less than 10 and not more than 20; the tailing factor for the idarubicin peak is not less than 0.85 and not more than 1.2; the column efficiency calculated from the idarubicin peak is not less than 3000 theoretical plates; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in µg, of C26H27NO9·HCl in each mg of the Idarubicin Hydrochloride taken by the formula:
100(C/M)(rU / rS)in which C is the concentration, in µg per mL, of idarubicin hydrochloride (C26H27NO9·HCl) in the Standard preparation; M is the quantity, in mg, of Idarubicin Hydrochloride taken to prepare the Assay preparation; and rU and rS are the responses of the idarubicin peak obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 3475Pharmacopeial Forum: Volume No. 27(6) Page 3302