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Fludrocortisone Acetate
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C23H31FO6 422.50

Pregn-4-ene-3,20-dione, 21-(acetyloxy)-9-fluoro-11,17-dihydroxy-, (11)-.
9-Fluoro-11,17,21-trihydroxypregn-4-ene-3,20-dione 21-acetate [514-36-3].
» Fludrocortisone Acetate contains not less than 97.0 percent and not more than 103.0 percent of C23H31FO6, calculated on the dried basis.
Packaging and storage— Preserve in well-closed containers, protected from light.
Identification, Infrared Absorption 197M.
Specific rotation 781S: between +126 and +138.
Test solution: 5 mg per mL, in acetone.
Loss on drying 731— Dry it in vacuum at 100 for 2 hours over magnesium perchlorate: it loses not more than 3.0% of its weight.
Residue on ignition 281: not more than 0.1%.
Chromatographic purity— Dissolve about 100 mg of it in a mixture of 5 mL of chloroform and 1 mL of acetone in a 10-mL volumetric flask, and dilute with chloroform to volume. Dilute 1 mL of this solution with chloroform to 100 mL. Apply 10 µL, in 5-µL increments, of the test solution and of its dilution to a line parallel to and about 2.5 cm from the bottom of a thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Develop the plate in a suitable chamber containing a mixture of chloroform, methanol, and water (85:14:1) until the solvent front has moved about 15 cm. Remove the plate, air-dry, and examine under short-wavelength UV light: no spot in the chromatogram of the more concentrated test solution, other than the principal spot, is larger or more intense than the spot from the diluted test solution (1.0%).
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay—
Standard preparation— Dissolve about 25 mg of USP Fludrocortisone Acetate RS, accurately weighed, in chloroform to make 250 mL, and mix. Pipet 10 mL of this solution into a 50-mL volumetric flask, add chloroform to volume, and mix.
Assay preparation— Prepare as directed under Standard preparation, using Fludrocortisone Acetate instead of the USP Reference Standard.
Procedure— Pipet 10 mL of the Assay preparation and the Standard preparation, respectively, into separate 25-mL volumetric flasks, and pipet 10 mL of chloroform into a third flask to provide a blank. Treat each flask as follows. Add 1.0 mL of a solution prepared by dissolving 50 mg of blue tetrazolium in 10 mL of methanol, and mix. Add 1.0 mL of a mixture of 1 volume of tetramethylammonium hydroxide TS and 4 volumes of methanol, mix, and allow to stand for 10 minutes. Dilute with a 1 in 100 solution of hydrochloric acid in methanol to volume. Concomitantly determine the absorbances of the solutions from the Assay preparation and the Standard preparation in 1-cm cells at about 525 nm, with a suitable spectrophotometer, against the reagent blank. Calculate the quantity, in mg, of C23H31FO6 in the portion of Fludrocortisone Acetate taken by the formula:
1.25C(AU / AS),
in which C is the concentration, in µg per mL, of USP Fludrocortisone Acetate RS in the Standard preparation; and AU and AS are the absorbances of the solutions from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Daniel K. Bempong, Ph.D., Scientist
Expert Committee : (MDPS05) Monograph Development-Pulmonary and Steroids
USP29–NF24 Page 917
Phone Number : 1-301-816-8143