Fludrocortisone Acetate
;)
Pregn-4-ene-3,20-dione,21-(acetyloxy)-9-fluoro-11,17-dihydroxy-,(11b)-.
9-Fluoro-11b,17,21-trihydroxypregn-4-ene-3,20-dione 21-acetate [514-36-3].
»Fludrocortisone Acetate contains not less than 97.0percent and not more than 103.0percent of C23H31FO6,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers,protected from light.
Identification,Infrared Absorption á197Mñ.
Specific rotation á781Sñ:
between +126
and +138.
and +138.
Test solution:
5mg per mL,in acetone.
Loss on drying á731ñ—
Dry it in vacuum at 100for 2hours over magnesium perchlorate:it loses not more than 3.0%of its weight.
for 2hours over magnesium perchlorate:it loses not more than 3.0%of its weight.
Residue on ignition á281ñ:
not more than 0.1%.
Chromatographic purity—
Dissolve about 100mg of it in a mixture of 5mLof chloroform and 1mLof acetone in a 10-mLvolumetric flask,and dilute with chloroform to volume.Dilute 1mLof this solution with chloroform to 100mL.Apply 10µL,in 5-µLincrements,of the test solution and of its dilution to a line parallel to and about 2.5cm from the bottom of a thin-layer chromatographic plate (see Chromatography á621ñ)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 15cm.Remove the plate,air-dry,and examine under short-wavelength UVlight: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%).
Assay—
Standard preparation—
Dissolve about 25mg of USP Fludrocortisone Acetate RS,accurately weighed,in chloroform to make 250mL,and mix.Pipet 10mLof this solution into a 50-mLvolumetric 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 10mLof the Assay preparationand the Standard preparation,respectively,into separate 25-mLvolumetric flasks,and pipet 10mLof chloroform into a third flask to provide a blank.Treat each flask as follows.Add 1.0mLof a solution prepared by dissolving 50mg of blue tetrazolium in 10mLof methanol,and mix.Add 1.0mLof a mixture of 1volume of tetramethylammonium hydroxide TSand 4volumes of methanol,mix,and allow to stand for 10minutes.Dilute with a 1in 100solution of hydrochloric acid in methanol to volume.Concomitantly determine the absorbances of the solutions from the Assay preparationand the Standard preparationin 1-cm cells at about 525nm,with a suitable spectrophotometer,against the reagent blank.Calculate the quantity,in mg,of C23H31FO6in the portion of Fludrocortisone Acetate taken by the formula:
1.25C(AU/AS),
in which Cis the concentration,in µg per mL,of USP Fludrocortisone Acetate RSin the Standard preparation,and AUand ASare the absorbances of the solutions from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 833
Phone Number:1-301-816-8139