Flumethasone Pivalate
;)
Pregna-1,4-diene-3,20-dione,21-(2,2-dimethyl-1-oxopropoxy)-6,9-difluoro-11,17-dihydroxy-16-methyl-,(6a,11b,16a)-.
6a,9-Difluoro-11b,17,21-trihydroxy-16a-methylpregna-1,4-diene-3,20-dione 21-pivalate [2002-29-1].
»Flumethasone Pivalate contains not less than 97.0percent and not more than 103.0percent of C27H36F2O6,calculated on the dried basis.
Packaging and storage—
Preserve in tight,light-resistant containers.
Identification—
A:
Infrared Absorption á197Mñ.
B:
Ultraviolet Absorption á197Uñ—
Solution:
20µg per mL.
Medium:
methanol.
Absorptivities at 237nm,calculated on the dried basis,do not differ by more than 3.0%.
Specific rotation á781Sñ:
between +71
and +82.
and +82.
Test solution:
10mg per mL,in dioxane.
Loss on drying á731ñ—
Dry it at 105for 4hours:it loses not more than 1.0%of its weight.
for 4hours:it loses not more than 1.0%of its weight.
Chromatographic purity—
Prepare a solution in dioxane containing 20mg per mL.Apply 5µLof this solution and 5µLeach of three dioxane solutions containing in each mL,respectively,200(1%),400(2%),and 600(3%)µg of USP Flumethasone Pivalate RSto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel.Allow the spots to dry,and develop the chromatogram in a solvent system consisting of toluene and ethyl acetate (7:3)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the solvent to evaporate.Locate the spots on the plate by lightly spraying with dilute sulfuric acid (1in 2),heating at 100for 30minutes,and inspecting under long-wavelength UVlight:the total content of any impurities detected,when compared to the Standard solutions,does not exceed 3.0%.
for 30minutes,and inspecting under long-wavelength UVlight:the total content of any impurities detected,when compared to the Standard solutions,does not exceed 3.0%.
Assay—
Standard preparation—
Dissolve a suitable quantity of USP Flumethasone Pivalate RS,accurately weighed,in alcohol,and dilute quantitatively and stepwise with alcohol to obtain a solution having a known concentration of about 20µg per mL.Transfer 10.0mLof this solution to a glass-stoppered,20-mLconical flask.
Assay preparation—
Transfer about 20mg of Flumethasone Pivalate,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with alcohol to volume,and mix.Transfer 10.0mLof this solution to a second 100-mLvolumetric flask,dilute with alcohol to volume,and mix.Transfer 10.0mLof this solution to a glass-stoppered,20-mLconical flask.
Procedure—
To each of the flasks containing the Standard preparationand the Assay preparation,and to a similar flask containing 10.0mLof alcohol to provide the blank,add 1.0mLof tetramethylammonium hydroxide TS.Mix,allow to stand for 20minutes,accurately timed,add 1.0mLof blue tetrazolium TSto each flask,and mix.Allow to stand for 40minutes,add 1.0mLof glacial acetic acid to each flask,mix,and concomitantly determine the absorbances of the solutions in 1-cm cells at the wavelength of maximum absorbance at about 520nm,with a suitable spectrophotometer,against the blank.Calculate the quantity,in mg,of C27H36F2O6in the portion of Flumethasone Pivalate taken by the formula:
C(AU/AS),
in which Cis the concentration,in µg per mL,of USP Flumethasone Pivalate 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 834
Phone Number:1-301-816-8139