U.S. PHARMACOPEIA

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Flumethasone Pivalate Cream
» Flumethasone Pivalate Cream contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of flumethasone pivalate (C27H36F2O6) in a suitable cream base.
Packaging and storage— Preserve in collapsible tubes.
Identification— Place a quantity of Cream, equivalent to about 400 µg of flumethasone pivalate, in a 50-mL centrifuge tube, and treat as directed in the Assay, collecting the extracts in a 50-mL centrifuge tube. Evaporate the acetonitrile on a water bath (about 75) with the aid of a stream of nitrogen. Dissolve the residue in 2.0 mL of acetonitrile with the aid of heat, allow to cool, and centrifuge. Apply 50 µL of this solution and 50 µL of a solution of chloroform and methanol (1:1) of USP Flumethasone Pivalate RS containing 200 µg per mL to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Allow the spots to dry, and develop the chromatogram in toluene 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. Redevelop the plate in the same manner in a solvent system consisting of toluene and ethyl acetate (7:3), remove the plate from the developing chamber, and allow the solvent to evaporate. Locate the spots on the plate by examination under short-wavelength UV light: the RF value of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.
Microbial limits 61— It meets the requirements of the tests for absence of Staphylococcus aureus and Pseudomonas aeruginosa.
Minimum fill 755: meets the requirements.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay—
Solvent acetonitrile— Saturate acetonitrile with isooctane.
Solvent isooctane— Saturate isooctane with acetonitrile.
4-Aminoantipyrine solution— Dissolve about 200 mg of 4-aminoantipyrine in a 1 in 100 solution of hydrochloric acid in methanol to make 50 mL of solution, and mix. Prepare this solution on the day of use.
Standard preparation— Dissolve a suitable quantity of USP Flumethasone Pivalate RS, accurately weighed, in Solvent acetonitrile, and dilute quantitatively and stepwise with Solvent acetonitrile to obtain a solution having a known concentration of about 40 µg per mL.
Assay preparation— Transfer an accurately weighed portion of Cream, equivalent to about 400 µg of flumethasone pivalate, to a tared glass-stoppered, 50-mL centrifuge tube. Place the tube in a vacuum desiccator, and dry the specimen in vacuum over silica gel until about 70% loss in weight is obtained.
Procedure— [NOTE—Perform the extractions in glass-stoppered, 50-mL centrifuge tubes with separation being effected by centrifugation, the portion to be retained being withdrawn into a hypodermic syringe fitted with a blunt-end, 14-gauge, 15-cm needle.] Add 10.0 mL of Solvent acetonitrile to the Assay preparation, and transfer 10.0 mL of the Standard preparation to a separate, glass-stoppered, 50-mL centrifuge tube. Add 25 mL of Solvent isooctane to each tube, shake by mechanical means until the cream is dispersed, and then shake both mixtures for 5 minutes. Separate and withdraw each acetonitrile layer, and filter through cotton pledgets, previously saturated with Solvent acetonitrile, into separate 25-mL volumetric flasks. Repeat the extraction, using a 10-mL portion of Solvent acetonitrile for each tube. Separate, withdraw, and filter each acetonitrile layer through the same respective filter, and combine the extracts with the main extracts. Dilute each with Solvent acetonitrile to volume, and mix. Transfer 10.0 mL of each solution to separate, glass-stoppered, 20-mL tubes, and to a third tube transfer 10.0 mL of Solvent acetonitrile to provide the blank. Evaporate the solvent on a water bath (about 75) with the aid of a stream of nitrogen. Add 5.0 mL of 4-Aminoantipyrine solution to each tube, insert the stopper, shake by mechanical means until the residue dissolves, and allow to stand for 1 hour. Concomitantly determine the absorbances of the solutions in 1-cm cells at the wavelength of maximum absorbance at about 390 nm, with a suitable spectrophotometer, against the blank. Calculate the quantity, in mg, of flumethasone pivalate (C27H36F2O6) in the portion of Cream taken by the formula:
0.01C(AU / AS),
in which C is the concentration, in µg per mL, of USP Flumethasone Pivalate 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 921
Phone Number : 1-301-816-8143