Pregna-1,4-diene-3,20-dione, 9-chloro-21-(2,2-dimethyl-1-oxopropoxy)-6-fluoro-11-hydroxy-16-methyl-, (6,11,16)-.
9-Chloro-6-fluoro-11,21-dihydroxy-16-methylpregna-1,4-diene-3,20-dione 21-pivalate [34097-16-0].
» Clocortolone Pivalate contains not less than 97.0 percent and not more than 103.0 percent of C27H36ClFO5, calculated on the dried basis.
Packaging and storage Preserve in tight, light-resistant containers.
Color and clarity of solution A 1 in 100 solution in chloroform is clear and practically colorless.
B: Ultraviolet Absorption 197U
Solution: 15 µg per mL.
Absorptivities at 238 nm, calculated on the dried basis, do not differ by more than 3.0%.
Specific rotation 781S: between +125 and +135.
Test solution: 40 mg per mL, in chloroform.
Loss on drying 731 Dry it at 105 for 3 hours: it loses not more than 1.0% of its weight.
Residue on ignition 281: not more than 0.2%, a 100-mg test specimen being used.
Test solution Accurately weigh about 100 mg of Clocortolone Pivalate, and transfer to a 25-mL volumetric flask. Dissolve in a mixture of chloroform and methanol (1:1), and dilute with the same solvent to volume.
Standard solution Using an accurately weighed quantity of USP Clocortolone Pivalate RS, prepare a solution in a mixture of chloroform and methanol (1:1) having a known concentration of about 4 mg per mL.
Procedure Score a 20- × 20-cm thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture into three equal sections to be used for the Test solution, the blank, and the Standard solution, respectively. Activate the plate at 105 for 30 minutes before use. Apply 100 µL each of the Test solution and the Standard solution as streaks 2.5 cm from the bottom of the appropriate section of the plate, and dry the streaks with a gentle current of air. Using a solvent system consisting of a mixture of cyclohexane and ethyl acetate (2:1), develop the chromatogram in a suitable chromatographic chamber lined with absorbent paper and previously equilibrated, until the solvent front has moved 15 cm above the line of application. Air-dry the plate, and develop the chromatogram a second time using the same chromatographic system. Air-dry the plate, and locate the principal band occupied by the Standard solution by viewing under UV light. Mark this band as well as corresponding bands in the blank and Test solution sections of the plate. Quantitatively remove the silica gel from each band, and transfer to separate glass-stoppered, 50-mL centrifuge tubes. Add 25.0 mL of methanol to each tube, shake for not less than 20 minutes, and centrifuge. Concomitantly determine the absorbances of the supernatants from the Test solution and the Standard solution against the blank at the wavelength of maximum absorbance at about 238 nm, with a suitable spectrophotometer. Calculate the percentage of chromatographic impurities in the Test solution taken by the formula:
100 [100(CS / CU)(AU / AS)]in which CS is the concentration, in mg per mL, of USP Clocortolone Pivalate RS in the Standard solution; CU is the concentration, in mg per mL, of the Test solution; and AU and AS are the absorbances of the solutions from the Test solution and the Standard solution, respectively: not more than 3.0% of total impurities is found.
Standard preparation Dissolve an accurately weighed quantity of USP Clocortolone Pivalate RS in chloroform to obtain a solution having a known concentration of about 0.75 mg per mL. Dilute an accurately measured volume of this solution with methanol, and mix to obtain a Standard preparation having a known concentration of about 30 µg per mL.
Assay preparation Accurately weigh about 75 mg of Clocortolone Pivalate, and transfer to a 100-mL volumetric flask. Dissolve in chloroform, dilute with chloroform to volume, and mix. Transfer 4.0 mL of this solution to a 100-mL volumetric flask, dilute with methanol to volume, and mix.
Procedure Transfer 10.0-mL portions of the Standard preparation and the Assay preparation to separate glass-stoppered, 50-mL conical flasks, and evaporate on a steam bath to dryness. To each flask, and to a third flask to provide the blank, add 15.0 mL of a solution containing 250 mg of isoniazid and 0.3 mL of hydrochloric acid in 500 mL of methanol. Swirl the contents of the flasks to dissolve the residues. Insert the stoppers securely in the flasks, and place in a water bath at 60 for 2.5 hours. Cool to room temperature. Concomitantly determine the absorbances of the Assay preparation and the Standard preparation in 1-cm cells against the blank at the wavelength of maximum absorbance at about 405 nm, with a suitable spectrophotometer. Calculate the quantity, in mg, of C27H36ClFO5 in the portion of Clocortolone Pivalate taken by the formula:
2.5C(AU / AS)in which C is the concentration, in µg per mL, of USP Clocortolone Pivalate RS in the Standard preparation, and AU and AS are the absorbances of the Assay preparation and the Standard preparation, respectively.
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USP32NF27 Page 1978